| CIR_vision_codex |
NOAEL |
>435 |
mg/kg bw |
rat |
oral |
4 weeks |
oral toxicity |
{"citation":"5; 0; 20","dose":"Groups of 5 rats were dosed with 0 or 3000 mg/kg bw of a neutralized 20% adipic acid solution orally, by gavage, for 4 weeks.49 A nonsignificant decrease in bw gain was observed.","effect":"ropsy at study termination. Groups of 5 rats were dosed with 0 or 3000 mg/kg bw of a neutralized 20% adipic acid solution orally, by gavage, for 4 weeks.49 A nonsignificant decrease in bw gain was observed. In a 4-week study in which a group of 3 rats was dosed orally, by gavage, with 2400 mg/kg bw adipic acid, no significant tox- icological effects were noted. In a 4-week dietary study in which groups of 17 to 20 female rats were fed 0 to 40 mg/d (0-435 mg/kg bw per d) adipic acid, no effects were reported.49 The no-observable adverse effect level (NOAEL) was >435 mg/kg bw per d. In a 5-week dietary study in which groups of 15 to 18 male rats were fed 0 to 800 mg/d (0-13 333 mg/kg bw/d) decreased bw gains, an unkempt appearance, and diarrhea were observed for the animals fed 800 mg/d the first 3 weeks. In another 5-week dietary study in which groups of 4 rats, gender not specified, were fed 100 or 200 mg/d (310-922 mg/kg bw/d) of a 20% adipic acid solution in ethanol, 5 days/week, no signs of toxicity were observed. Ten rats were dosed orally, method not specified, with 199 mg/d...","page":14,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_001"} |
| CIR_vision_codex |
NOAEL |
=3333 |
mg/kg bw |
rat |
oral |
19 weeks |
oral toxicity |
{"citation":"8; 10; 0, 420, 840","dose":"Groups of 8 to 10 male rats were given 0, 420, 840, 1700, or 3400 mg/kg bw/d sodium adipate for 19 weeks in a protein deficient diet.57 Animals were killed after either 7 weeks or at study termination.","effect":"Groups of 8 to 10 male rats were given 0, 420, 840, 1700, or 3400 mg/kg bw/d sodium adipate for 19 weeks in a protein deficient diet.57 Animals were killed after either 7 weeks or at study termination. For unexplained reasons, only 5 to 7 animals/group survived until study termination. Rats of the 3400 mg/kg bw/d group had decreased bw gains and decreased bws. (Statistical significance not stated.) Slight effects were seen in the liver, and the NOAEL was 3333 mg/kg bw. Groups of 13 to 15 male and female rats were fed a diet containing 0, 1600, or 3200 mg/kg bw/d adipic acid for 33 weeks.40 Rats were killed at various intervals throughout the study. Ten of 14 rats fed 3200 mg/kg bw/d died during weeks 0 to 4; surviving rats had decreased weight gains during this time. However, at study termination, bws were for surviving animals of this group were similar to controls. Slight effects were seen in the liver. (Statistical significance not stated.) In a 2-year study, groups of 20 male rats were fed a diet containing 0%, 0.1%, 1%, 3%, and 5% adipic acid (equiv. to 0, 75, 750, 2250, a","page":16,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_002"} |
| CIR_vision_codex |
NOAEL |
=1 |
% |
rat |
oral |
2-year |
inhalation toxicity |
{"citation":"2; 20; 0","dose":"(Statistical significance not stated.) In a 2-year study, groups of 20 male rats were fed a diet containing 0%, 0.1%, 1%, 3%, and 5% adipic acid (equiv. to 0, 75, 750, 2250, and 3750 mg/kg bw/d), and groups of 10 and 19 females were fed 0% and 1% adipic acid, respectively.49 Weight gains of male rats fed 3% and 5% adipic acid were significantly less than...","effect":"imilar to controls. Slight effects were seen in the liver. (Statistical significance not stated.) In a 2-year study, groups of 20 male rats were fed a diet containing 0%, 0.1%, 1%, 3%, and 5% adipic acid (equiv. to 0, 75, 750, 2250, and 3750 mg/kg bw/d), and groups of 10 and 19 females were fed 0% and 1% adipic acid, respectively.49 Weight gains of male rats fed 3% and 5% adipic acid were significantly less than controls. There were no significant tox- icological findings upon gross or microscopic observation. The NOAEL was 1% adipic acid for male and female rats. The effect of adipic acid on hepatic peroxisome prolifera- tion was evaluated in an in vivo study in which 4 male F344 rats were fed chow containing 2% adipic acid dissolved in alcohol.67 After 3 weeks of dosing, the animals were killed. Adipic acid did not induce peroxisome proliferation and did not affect relative liver to bws. Inhalation Mice were exposed to 460 mg/m3 adipic acid dust for 1.5 mos, or to 13 or 129 mg/m3 adipic acid for 4 mos (details not given).40 Decreased weight gain, altered oxidase activity, and up...","page":16,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_003"} |
| CIR_vision_codex |
NOAEL |
=2 |
% |
rat |
oral |
90 days |
repeated dose toxicity |
{"citation":"1; 2; 4","dose":"Groups of 15 male and 15 female rats were dosed orally, by gavage, for 90 days with 0% to 30% of a mixture that contained 4% adipic, 16% glutaric, and 5% succinic acid.55 The vehicle was deionized water, and the dosing volume was 10 mL/kg.","effect":"al chemistry, or urinalysis. There were no microscopic findings or organ weight changes attribu- table to the test substance. There was no treatment-related mortality. The NOAEL was \u00061%, and the LOAEL was 2% glutaric acid. Four male and 4 female Beagle dogs were fed a diet contain- ing 0% to 5% glutaric acid for 90 days.68 Decreased bws, accompanied by reduced feed consumption, were observed for the males and females of the 5% group and females of the 3% group. No other treatment-related effects were observed. The NOAEL was \u00062% and the LOAEL was 3%. Adipic/glutaric/succinic acid mixture. Groups of 15 male and 15 female rats were dosed orally, by gavage, for 90 days with 0% to 30% of a mixture that contained 4% adipic, 16% glutaric, and 5% succinic acid.55 The vehicle was deionized water, and the dosing volume was 10 mL/kg. Two males and 1 female of the 30% group died, and the deaths were considered dose- related. Also in this group, bws were reduced for males and females, and feed consumption was statistically significantly reduced in males. An increased incidence of labored breat...","page":17,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_004"} |
| CIR_vision_codex |
NOAEL |
=3 |
% |
rat |
oral |
180 days |
oral toxicity |
{"citation":"30; 10; 3","dose":"deaths were considered dose- related.","effect":"deaths were considered dose- related. Also in this group, bws were reduced for males and females, and feed consumption was statistically significantly reduced in males. An increased incidence of labored breathing and rales was noted. The urine pH was statistically significantly reduced in both males and females dosed with 30% of the mixture. In the 10% group, bw gains were slightly, but not statistically significantly, reduced in females and feed con- sumption was statistically significantly reduced in males. The NOAEL was 3% and the LOAEL was 10%. Azelaic acid. Groups of 15 male and 15 female Wistar rats were fed a diet containing 140 or 280 mg/kg bw azelaic acid for 180 days, and a control group of 10 males and 10 females was given untreated feed.59 No significant toxicological effects were observed. Growth was similar between test and control groups, as were the microscopic examinations and clinical chemistry parameters. The researchers found similar, negative, results when groups of 10 male and 10 female New Zealand rabbits were fed diets containing 0, 200, or 400 mg/kg bw aze...","page":17,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_005"} |
| CIR_vision_codex |
NOAEL |
=263 |
mg/kg bw |
rat |
oral |
- |
developmental toxicity |
{"citation":"6; 15; 38","dose":"No reproductive, developmental, or maternal effects were observed, and the NOAEL for mater- nal and developmental toxicity was 263 mg/kg bw.","effect":"adipic acid on days 6 to 15 of gestation.38 All animals were killed on day 17 of gestation. No reproductive, developmental, or maternal effects were observed, and the NOAEL for mater- nal and developmental toxicity was 263 mg/kg bw. Similar results were obtained in a study in which gravid Wistar rats were dosed orally, by gavage, with 0, 2.9, 13, 62, or 288 mg/kg bw adipic acid on days 6 to 15 of gestation. The NOAEL for maternal and developmental toxicity was 288 mg/kg bw.38 Groups of 21 to 24 gravid hamsters were dosed orally, by gavage, with 0, 2.9, 5, 44, or 205 mg/kg bw adipic acid on days 6 to 10 of gestation. A significant increase in resorption per implant site was observed with 205 mg/kg bw adipic acid, resulting in a decreased number of live fetuses. (This decrease was not evaluated statisti","page":21,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_006"} |
| CIR_vision_codex |
NOAEL |
=288 |
mg/kg bw |
rat |
oral |
- |
developmental toxicity |
{"citation":"6; 15; 38","dose":"No reproductive, developmental, or maternal effects were observed, and the NOAEL for mater- nal and developmental toxicity was 263 mg/kg bw.","effect":"adipic acid on days 6 to 15 of gestation.38 All animals were killed on day 17 of gestation. No reproductive, developmental, or maternal effects were observed, and the NOAEL for mater- nal and developmental toxicity was 263 mg/kg bw. Similar results were obtained in a study in which gravid Wistar rats were dosed orally, by gavage, with 0, 2.9, 13, 62, or 288 mg/kg bw adipic acid on days 6 to 15 of gestation. The NOAEL for maternal and developmental toxicity was 288 mg/kg bw.38 Groups of 21 to 24 gravid hamsters were dosed orally, by gavage, with 0, 2.9, 5, 44, or 205 mg/kg bw adipic acid on days 6 to 10 of gestation. A significant increase in resorption per implant site was observed with 205 mg/kg bw adipic acid, resulting in a decreased number of live fetuses. (This decrease was not evaluated statistically.) No other effects were reported.38 Groups of 10 to 14 gravid Dutch-belted rabbits were dosed by oral intubation with 0, 2.5, 12, 54, or 250 mg/kg bw adipic acid on days 6 to 18 of gestation. No reproductive, develop- mental, or maternal effe","page":21,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_007"} |
| CIR_vision_codex |
NOAEL |
=250 |
mg/kg bw |
rat |
oral |
- |
developmental toxicity |
{"citation":"4; 205; 6","dose":"4, or 205 mg/kg bw adipic acid on days 6 to 10 of gestation.","effect":"4, or 205 mg/kg bw adipic acid on days 6 to 10 of gestation. A significant increase in resorption per implant site was observed with 205 mg/kg bw adipic acid, resulting in a decreased number of live fetuses. (This decrease was not evaluated statistically.) No other effects were reported.38 Groups of 10 to 14 gravid Dutch-belted rabbits were dosed by oral intubation with 0, 2.5, 12, 54, or 250 mg/kg bw adipic acid on days 6 to 18 of gestation. No reproductive, develop- mental, or maternal effects were observed. The NOAEL for maternal toxicity was \u0006250 mg/kg bw and for developmental toxicity was 250 mg/kg bw.38 Azelaic Acid. Reproductive and teratogenic effects of azelaic acid were evaluated using Wistar rats and New Zealand rab- bits.57 A group of 20 gravid rats was fed a diet containing 140 mg/kg bw/d azelaic acid, and a control group of 10 gravid rats was given untreated feed. Half of each group was killed and necropsied on day 19 of gestation, and the remaining animals continued dosing for 3 mos. The day of gestation that dosing started is not clear. No gross or microscopic lesi...","page":21,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_008"} |
| CIR_vision_codex |
NOAEL |
=1000 |
mg/kg bw |
rat |
- |
- |
developmental toxicity |
{"citation":"0; 54; 35","dose":"The reproductive toxicity of 0 to 1000 mg/kg bw dodecanedioic acid was evaluated in an OECD com- bined repeated doe and reproductive/developmental toxicity screening test using male and female Crl:CD:BR rats.54 The no-observable effect level (NOEL) for reproductive and devel- opmental toxicity was 1000 mg/kg bw.","effect":"sing started is not clear. No gross or microscopic lesions were observed for the uteri, pla- centas, or ovaries. There were no differences in reproductive or developmental effects between treated and control groups, nor were there any differences in fetal weights of the live fetuses. Dodecanedioic Acid. The reproductive toxicity of 0 to 1000 mg/kg bw dodecanedioic acid was evaluated in an OECD com- bined repeated doe and reproductive/developmental toxicity screening test using male and female Crl:CD:BR rats.54 The no-observable effect level (NOEL) for reproductive and devel- opmental toxicity was 1000 mg/kg bw. Sodium Salt of Adipic, Azelaic, Sebacic, and Dodecanedioic Acids. The influence of the sodium salt of some dicarboxylic acids (adipic acid, azelaic acid, sebacic acid, dodecanedioic acid) on both spontaneous and evoked muscle activity of the uterine horns of 35 female Wistar rats (250-300 g) has been studied in vitro.68 Spontaneous activity of uterine muscle was inhibited by dicarboxylic salts causing the total abolition of mechanical events at concentrations of 24, 32, 40,...","page":21,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_009"} |
| CIR_vision_codex |
NOAEL |
=200 |
mg/kg bw |
rat |
- |
4 weeks |
NOAEL study |
{"citation":"200; 4","dose":"In the ovary, an increase in atresia of the large follicle and a decrease in currently formed corpora lutea were seen in animals dosed with 1000 and 2000 mg/kg bw, and in the 2000 mg/kg bw group, an increase in follicular cysts was observed.","effect":"and a statistically significant decrease in the relative weight of the left ovary. Microscopi- cally, abnormal findings were reported for both the ovary and kidney. In the ovary, an increase in atresia of the large follicle and a decrease in currently formed corpora lutea were seen in animals dosed with 1000 and 2000 mg/kg bw, and in the 2000 mg/kg bw group, an increase in follicular cysts was observed. In the kidney, an eosinophilic change of the proximal tubule was observed for the 2000 mg/kg bw dose group. The NOAEL was 200 mg/kg bw. In the rats dosed for 4 weeks, similar observations were made. There was staining around the perineum of animals dosed with 1000 and 2000 mg/kg bw diethylhexyl adipate, and final bws of animals dosed with 2000 mg/kg bw were statisti- cally significantly decreased. The relative kidney to bws were statistically significantly increased in animals at all dose levels, and liver weights were statistically significantly increased in animals of the 1000 and 2000 mg/kg bw dose groups. The mean estrous cycle length was statistically significantly decreased i...","page":41,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_010"} |
| CIR_vision_codex |
NOAEL |
=610 |
mg/kg bw |
rat |
oral |
90-day |
repeated dose toxicity |
{"citation":"2; 90; 10","dose":"With the excep- tion of decreased weight gain for some of the groups, no compound-related toxicologic effects were observed.2 In a 90-day dietary study, groups of 10 rats per group were fed 0 to 4740 mg/kg bw diethylhexyl adipate for 90 days.113 Mortality occurred in the 4740 mg/kg bw group, but the num- ber of deaths was not specified.","effect":"ethylhexyl adipate. With the excep- tion of decreased weight gain for some of the groups, no compound-related toxicologic effects were observed.2 In a 90-day dietary study, groups of 10 rats per group were fed 0 to 4740 mg/kg bw diethylhexyl adipate for 90 days.113 Mortality occurred in the 4740 mg/kg bw group, but the num- ber of deaths was not specified. Decreased growth and feed consumption was reported for animals fed 2920 mg/kg bw. Changes in kidney and liver weights were noted, but no details were given. The NOEL was 610 mg/kg bw, and the LOEL was 2920 mg/kg bw diethylhexyl adipate. Groups of 15 male and 15 female Sprague Dawley rats were fed 0 or 2.5% diethylhexyl adipate for 90 days.92 At study termination, all animals were killed for necropsy. Body weight gains were statistically significantly decreased for treated males and females, and relative kidney and liver to bws were statistically significantly increased for treated females, when compared to controls. In a 13-week dietary study in which groups of 5 to 8 rats and mice were fed diets containing 0% to 4.0% and 0% to...","page":41,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_011"} |
| CIR_vision_codex |
NOAEL |
<4000 |
mg/kg |
rat |
- |
- |
NOAEL study |
{"citation":"9; 1; 92","dose":"specified 9.1 g/kg 92 Diisooctyl Adipate rats 5/group 2000-64 000 mg/kg, undiluted greater than highest dose tested 92 guinea pigs not specified not specified >5 mL/kg 92 Diisononyl Adipate rats 5/group 346-10 000 mg/kg, undiluted greater than highest dose tested 92 Diisodecyl Adipate NMRI mice 5 male 2000 mg/kg greater than highest dose tested 114 rats n...","effect":"specified 9.1 g/kg 92 Diisooctyl Adipate rats 5/group 2000-64 000 mg/kg, undiluted greater than highest dose tested 92 guinea pigs not specified not specified >5 mL/kg 92 Diisononyl Adipate rats 5/group 346-10 000 mg/kg, undiluted greater than highest dose tested 92 Diisodecyl Adipate NMRI mice 5 male 2000 mg/kg greater than highest dose tested 114 rats not specified undiluted 20 500 mg/kg 92 Dioctyldodecyl Adipate NMRI mice 5 female 2000 mg/kg greater than highest dose tested 115 rats not specified not specified NOAEL <4000 mg/kg 35 Diisocetyl Adipate NMRI mice 5 males 2000 mg/kg greater than highest dose tested 116 Diisopropyl Sebacate NMRI mice 5 female 2000 mg/kg greater than highest dose tested 117 Diethylhexyl Sebacate NMRI mice 5 female 2000 mg/kg greater than highest dose tested 118 mice not specified undiluted 9.5 g/kg 92 (continued) 46S International Journal of Toxicology 31(Supplement 1)","page":42,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_012"} |
| CIR_vision_codex |
NOAEL |
>8000 |
mg/kg |
rat |
dermal |
- |
NOAEL study |
{"citation":"111; 9; 121","dose":"kg 111 Isooctyl Alcohol (metabolite of diisooctyl adipate and diisooctyl sebacate) rats mixture of C7-9 branched alkyl alcohols >2000 mg/kg 121 Nonyl Alcohol (metabolite of diisononyl adipate) rats mixture of C8-10 branched alkyl alcohols 3000 mg/kg 121 Isodecyl Alcohol (metabolite of diisodecyl adipate) rats mixture of C9-11 branched alkyl alcohols 4600...","effect":"kg 111 Isooctyl Alcohol (metabolite of diisooctyl adipate and diisooctyl sebacate) rats mixture of C7-9 branched alkyl alcohols >2000 mg/kg 121 Nonyl Alcohol (metabolite of diisononyl adipate) rats mixture of C8-10 branched alkyl alcohols 3000 mg/kg 121 Isodecyl Alcohol (metabolite of diisodecyl adipate) rats mixture of C9-11 branched alkyl alcohols 4600 mg/kg 121 DERMAL Diethyl Malonate rabbits not specified not specified 16 700 mg/kg 39 Dibutyl Adipate rabbits not specified 96% 20 mL/kg 5 rats not specified i.m. NOAEL >8000 mg/kg 122 Ditridecyl Adipate rabbits 3 2000 mg/kg greater than highest dose tested 92 rabbits 10 5000 m/kg to abraded skin; semi- occlusive greater than highest dose tested 92 Diethylhexyl Adipate rabbits 8 \u00058700 m/kg to abraded skin; occlusive mild irritation; no systemic toxic effects 2 rabbits 1 male/1 female \u00058660 mg/kg for 24 hours, occluded, 1 intact and 1 abraded site >8670 mg/kg 113 Diisononyl Adipate rabbits 4/group 50-3160 mg/kg to abraded skin greater than highest dose tested 92 Diethylhexyl Sebacate guinea pigs not specified not specified <10 000...","page":43,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_013"} |
| CIR_vision_codex |
NOAEL |
=500 |
mg/kg bw/d |
rat |
oral |
13 weeks |
repeated dose toxicity |
{"citation":"10; 0, 50, 150; 500","dose":"Groups of 10 male and 10 female rats were fed 0, 50, 150, or 500 mg/kg bw diisononyl adipate for 13 weeks.92 A statistically significant increase in relative kid- ney to bws was reported for males and females given 500 mg/ kg bw, but absolute kidney weights were not affected and no significant microscopic effects were seen.","effect":"te. Groups of 10 male and 10 female rats were fed 0, 50, 150, or 500 mg/kg bw diisononyl adipate for 13 weeks.92 A statistically significant increase in relative kid- ney to bws was reported for males and females given 500 mg/ kg bw, but absolute kidney weights were not affected and no significant microscopic effects were seen. Microscopic changes in any of the organs, including the testes and epididy- mis of males and ovaries of females, were not observed. There were no significant toxicological findings, and the NOAEL was 500 mg/kg bw/d. In another 13-week study, groups of 4 male and 4 female Beagle dogs were fed 0, 0.3, 1.0, or 3.0% diisononyl adipate; the high dose was increased to 6% during weeks 9 to 13.92 No significant findings were reported for the 0.3 or 1.0% groups. In the high-dose group, decreased bws, testes weight, and feed consumption, increased liver weights, elevated enzyme levels, liver and kidney discoloration, and microscopic changes in the liver, testes, spleen, and kidneys were reported. The dietary NOAEL for diisononyl adipate was 1.0%. Ditridecyl adipate....","page":45,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_014"} |
| CIR_vision_codex |
NOAEL |
=300 |
mg/kg bw |
rat |
- |
- |
developmental toxicity |
{"citation":"100; 300; 5","dose":"In the 100 mg/kg bw group, a statistically significant decrease in the number of live pups was due to an increase in post-implantation loss.","effect":"yl malonate. This effect was not observed in the recovery animals or in the other test groups. No other signifi- cant toxicological effects were observed. Performance in a functional observation battery was similar for test and control animals. There was no effect on fertility. In the 100 mg/kg bw group, a statistically significant decrease in the number of live pups was due to an increase in post-implantation loss. This effect was not considered treatment related, and no develop- mental toxicity was reported. The NOAEL was 300 mg/kg bw for repeated doses and maternal toxicity and 1000 mg/kg bw for fertility and developmental toxicity. Dimethyl Adipate. Groups of 5 gravid Sprague Dawley rats were dosed ip with 0.0603 to 0.6028 mL/kg dimethyl adipate (1/30, 1/10, 1/5, and 1/3 of the ip LD50 value) on days 5, 10, and 15 of gestation.124 A pooled volume control consisted of ani- mals dosed with 10 mL/kg distilled water, saline, or cottonseed oil. A positive control group was not used. All animals were killed and examined on day 20 of gestation. The mean fetal weights and the numbers...","page":53,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_016"} |
| CIR_vision_codex |
NOAEL |
=2000 |
mg/kg bw/d |
rat |
- |
5 days |
developmental toxicity |
{"citation":"0; 3; 16","dose":"Weight gains were statistically sig- nificantly decreased for the 2000 mg/kg bw group during days 0 to 3 and 16 to 20 of gestation.","effect":"imals. No mater- nal mortality was reported. Weight gains were statistically sig- nificantly decreased for the 2000 mg/kg bw group during days 0 to 3 and 16 to 20 of gestation. Weight gains were statistically significantly decreased in the 800 mg/kg bw group during days 0 to 3 of gestation. No differences in skeletal anomalies were observed, but there were some differences in visceral anomalies, including increased incidence of levocardia at 2000 mg/kg bw. These anomalies were not considered treatment-related. The NOAEL for maternal toxicity was 2000 mg/kg bw/d, and for developmental and reproductive effects it was 800 mg/kg bw/d. Groups of 25 mated female rats were dosed dermally with 0 and 2000 mg/kg bw ditridecyl adipate following the same study protocol as above. Again, there were no signs of maternal toxicity. No developmental toxicity was reported, and there were no visceral anomalies or levocardia. Tridecyl adipate, 2000 mg/kg bw, was applied, unoccluded, to groups of 10 male Sprague-Dawley rats, 5 days/week for 13 weeks, and the effect on sperm morphology was evaluated.92...","page":54,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_017"} |
| CIR_vision_codex |
NOAEL |
=170 |
mg/kg bw/d |
- |
oral |
10 weeks |
developmental toxicity |
{"citation":"28, 170; 10; 92","dose":"adipate (calcu- lated as 28, 170, or 1080 mg/kg bw/d) for 10 weeks prior to mating.92 Dosing was terminated, and the animals were mated.","effect":"adipate (calcu- lated as 28, 170, or 1080 mg/kg bw/d) for 10 weeks prior to mating.92 Dosing was terminated, and the animals were mated. (A different source indicated that dosing continued throughout the study).161 A reduction in bw gain was reported during gestation for the dams of the 1.2% group. No test article- related effects on fertility were observed. Fetal weight, total litter weight, and litter size were reduced in the 1.2% group, but the number of pups born live, or their survival, was not affected. The NOAEL was 170 mg/kg bw/d and the LOAEL was 1080 mg/kg bw/d. In another study in which gravid females were fed the same doses as above on days 1 to 22 of gestation, maternal bw and feed consumption were statistically decreased in the 1.2% group. No significant effects on fetal weight or litter size were reported. Animals of the 0.18 and 1.2% groups had slightly increased incidences of minor skeletal abnormalities; this increase was attributed to fetotoxicity. The NOEL for maternal toxicity was 170 mg/kg bw/d. The NOAELs for developmental toxicity and fetotoxicity were 170...","page":55,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_018"} |
| CIR_vision_codex |
NOAEL |
>435 |
mg/kg bw |
rat |
oral |
4 weeks |
oral toxicity |
{"citation":"5; 0; 20","dose":"Groups of 5 rats were dosed with 0 or 3000 mg/kg bw of a neutralized 20% adipic acid solution orally, by gavage, for 4 weeks.49 A nonsignificant decrease in bw gain was observed.","effect":"ropsy at study termination. Groups of 5 rats were dosed with 0 or 3000 mg/kg bw of a neutralized 20% adipic acid solution orally, by gavage, for 4 weeks.49 A nonsignificant decrease in bw gain was observed. In a 4-week study in which a group of 3 rats was dosed orally, by gavage, with 2400 mg/kg bw adipic acid, no significant tox- icological effects were noted. In a 4-week dietary study in which groups of 17 to 20 female rats were fed 0 to 40 mg/d (0-435 mg/kg bw per d) adipic acid, no effects were reported.49 The no-observable adverse effect level (NOAEL) was >435 mg/kg bw per d. In a 5-week dietary study in which groups of 15 to 18 male rats were fed 0 to 800 mg/d (0-13 333 mg/kg bw/d) decreased bw gains, an unkempt appearance, and diarrhea were observed for the animals fed 800 mg/d the first 3 weeks. In another 5-week dietary study in which groups of 4 rats, gender not specified, were fed 100 or 200 mg/d (310-922 mg/kg bw/d) of a 20% adipic acid solution in ethanol, 5 days/week, no signs of toxicity were observed. Ten rats were dosed orally, method not specified, with 199 mg/d...","page":14,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_001"} |
| CIR_vision_codex |
NOAEL |
=3333 |
mg/kg bw |
rat |
oral |
19 weeks |
oral toxicity |
{"citation":"8; 10; 0, 420, 840","dose":"Groups of 8 to 10 male rats were given 0, 420, 840, 1700, or 3400 mg/kg bw/d sodium adipate for 19 weeks in a protein deficient diet.57 Animals were killed after either 7 weeks or at study termination.","effect":"Groups of 8 to 10 male rats were given 0, 420, 840, 1700, or 3400 mg/kg bw/d sodium adipate for 19 weeks in a protein deficient diet.57 Animals were killed after either 7 weeks or at study termination. For unexplained reasons, only 5 to 7 animals/group survived until study termination. Rats of the 3400 mg/kg bw/d group had decreased bw gains and decreased bws. (Statistical significance not stated.) Slight effects were seen in the liver, and the NOAEL was 3333 mg/kg bw. Groups of 13 to 15 male and female rats were fed a diet containing 0, 1600, or 3200 mg/kg bw/d adipic acid for 33 weeks.40 Rats were killed at various intervals throughout the study. Ten of 14 rats fed 3200 mg/kg bw/d died during weeks 0 to 4; surviving rats had decreased weight gains during this time. However, at study termination, bws were for surviving animals of this group were similar to controls. Slight effects were seen in the liver. (Statistical significance not stated.) In a 2-year study, groups of 20 male rats were fed a diet containing 0%, 0.1%, 1%, 3%, and 5% adipic acid (equiv. to 0, 75, 750, 2250, a","page":16,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_002"} |
| CIR_vision_codex |
NOAEL |
=1 |
% |
rat |
oral |
2-year |
inhalation toxicity |
{"citation":"2; 20; 0","dose":"(Statistical significance not stated.) In a 2-year study, groups of 20 male rats were fed a diet containing 0%, 0.1%, 1%, 3%, and 5% adipic acid (equiv. to 0, 75, 750, 2250, and 3750 mg/kg bw/d), and groups of 10 and 19 females were fed 0% and 1% adipic acid, respectively.49 Weight gains of male rats fed 3% and 5% adipic acid were significantly less than...","effect":"imilar to controls. Slight effects were seen in the liver. (Statistical significance not stated.) In a 2-year study, groups of 20 male rats were fed a diet containing 0%, 0.1%, 1%, 3%, and 5% adipic acid (equiv. to 0, 75, 750, 2250, and 3750 mg/kg bw/d), and groups of 10 and 19 females were fed 0% and 1% adipic acid, respectively.49 Weight gains of male rats fed 3% and 5% adipic acid were significantly less than controls. There were no significant tox- icological findings upon gross or microscopic observation. The NOAEL was 1% adipic acid for male and female rats. The effect of adipic acid on hepatic peroxisome prolifera- tion was evaluated in an in vivo study in which 4 male F344 rats were fed chow containing 2% adipic acid dissolved in alcohol.67 After 3 weeks of dosing, the animals were killed. Adipic acid did not induce peroxisome proliferation and did not affect relative liver to bws. Inhalation Mice were exposed to 460 mg/m3 adipic acid dust for 1.5 mos, or to 13 or 129 mg/m3 adipic acid for 4 mos (details not given).40 Decreased weight gain, altered oxidase activity, and up...","page":16,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_003"} |
| CIR_vision_codex |
NOAEL |
=2 |
% |
rat |
oral |
90 days |
repeated dose toxicity |
{"citation":"1; 2; 4","dose":"Groups of 15 male and 15 female rats were dosed orally, by gavage, for 90 days with 0% to 30% of a mixture that contained 4% adipic, 16% glutaric, and 5% succinic acid.55 The vehicle was deionized water, and the dosing volume was 10 mL/kg.","effect":"al chemistry, or urinalysis. There were no microscopic findings or organ weight changes attribu- table to the test substance. There was no treatment-related mortality. The NOAEL was \u00061%, and the LOAEL was 2% glutaric acid. Four male and 4 female Beagle dogs were fed a diet contain- ing 0% to 5% glutaric acid for 90 days.68 Decreased bws, accompanied by reduced feed consumption, were observed for the males and females of the 5% group and females of the 3% group. No other treatment-related effects were observed. The NOAEL was \u00062% and the LOAEL was 3%. Adipic/glutaric/succinic acid mixture. Groups of 15 male and 15 female rats were dosed orally, by gavage, for 90 days with 0% to 30% of a mixture that contained 4% adipic, 16% glutaric, and 5% succinic acid.55 The vehicle was deionized water, and the dosing volume was 10 mL/kg. Two males and 1 female of the 30% group died, and the deaths were considered dose- related. Also in this group, bws were reduced for males and females, and feed consumption was statistically significantly reduced in males. An increased incidence of labored breat...","page":17,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_004"} |
| CIR_vision_codex |
NOAEL |
=3 |
% |
rat |
oral |
180 days |
oral toxicity |
{"citation":"30; 10; 3","dose":"deaths were considered dose- related.","effect":"deaths were considered dose- related. Also in this group, bws were reduced for males and females, and feed consumption was statistically significantly reduced in males. An increased incidence of labored breathing and rales was noted. The urine pH was statistically significantly reduced in both males and females dosed with 30% of the mixture. In the 10% group, bw gains were slightly, but not statistically significantly, reduced in females and feed con- sumption was statistically significantly reduced in males. The NOAEL was 3% and the LOAEL was 10%. Azelaic acid. Groups of 15 male and 15 female Wistar rats were fed a diet containing 140 or 280 mg/kg bw azelaic acid for 180 days, and a control group of 10 males and 10 females was given untreated feed.59 No significant toxicological effects were observed. Growth was similar between test and control groups, as were the microscopic examinations and clinical chemistry parameters. The researchers found similar, negative, results when groups of 10 male and 10 female New Zealand rabbits were fed diets containing 0, 200, or 400 mg/kg bw aze...","page":17,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_005"} |
| CIR_vision_codex |
NOAEL |
=263 |
mg/kg bw |
rat |
oral |
- |
developmental toxicity |
{"citation":"6; 15; 38","dose":"No reproductive, developmental, or maternal effects were observed, and the NOAEL for mater- nal and developmental toxicity was 263 mg/kg bw.","effect":"adipic acid on days 6 to 15 of gestation.38 All animals were killed on day 17 of gestation. No reproductive, developmental, or maternal effects were observed, and the NOAEL for mater- nal and developmental toxicity was 263 mg/kg bw. Similar results were obtained in a study in which gravid Wistar rats were dosed orally, by gavage, with 0, 2.9, 13, 62, or 288 mg/kg bw adipic acid on days 6 to 15 of gestation. The NOAEL for maternal and developmental toxicity was 288 mg/kg bw.38 Groups of 21 to 24 gravid hamsters were dosed orally, by gavage, with 0, 2.9, 5, 44, or 205 mg/kg bw adipic acid on days 6 to 10 of gestation. A significant increase in resorption per implant site was observed with 205 mg/kg bw adipic acid, resulting in a decreased number of live fetuses. (This decrease was not evaluated statisti","page":21,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_006"} |
| CIR_vision_codex |
NOAEL |
=288 |
mg/kg bw |
rat |
oral |
- |
developmental toxicity |
{"citation":"6; 15; 38","dose":"No reproductive, developmental, or maternal effects were observed, and the NOAEL for mater- nal and developmental toxicity was 263 mg/kg bw.","effect":"adipic acid on days 6 to 15 of gestation.38 All animals were killed on day 17 of gestation. No reproductive, developmental, or maternal effects were observed, and the NOAEL for mater- nal and developmental toxicity was 263 mg/kg bw. Similar results were obtained in a study in which gravid Wistar rats were dosed orally, by gavage, with 0, 2.9, 13, 62, or 288 mg/kg bw adipic acid on days 6 to 15 of gestation. The NOAEL for maternal and developmental toxicity was 288 mg/kg bw.38 Groups of 21 to 24 gravid hamsters were dosed orally, by gavage, with 0, 2.9, 5, 44, or 205 mg/kg bw adipic acid on days 6 to 10 of gestation. A significant increase in resorption per implant site was observed with 205 mg/kg bw adipic acid, resulting in a decreased number of live fetuses. (This decrease was not evaluated statistically.) No other effects were reported.38 Groups of 10 to 14 gravid Dutch-belted rabbits were dosed by oral intubation with 0, 2.5, 12, 54, or 250 mg/kg bw adipic acid on days 6 to 18 of gestation. No reproductive, develop- mental, or maternal effe","page":21,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_007"} |
| CIR_vision_codex |
NOAEL |
=250 |
mg/kg bw |
rat |
oral |
- |
developmental toxicity |
{"citation":"4; 205; 6","dose":"4, or 205 mg/kg bw adipic acid on days 6 to 10 of gestation.","effect":"4, or 205 mg/kg bw adipic acid on days 6 to 10 of gestation. A significant increase in resorption per implant site was observed with 205 mg/kg bw adipic acid, resulting in a decreased number of live fetuses. (This decrease was not evaluated statistically.) No other effects were reported.38 Groups of 10 to 14 gravid Dutch-belted rabbits were dosed by oral intubation with 0, 2.5, 12, 54, or 250 mg/kg bw adipic acid on days 6 to 18 of gestation. No reproductive, develop- mental, or maternal effects were observed. The NOAEL for maternal toxicity was \u0006250 mg/kg bw and for developmental toxicity was 250 mg/kg bw.38 Azelaic Acid. Reproductive and teratogenic effects of azelaic acid were evaluated using Wistar rats and New Zealand rab- bits.57 A group of 20 gravid rats was fed a diet containing 140 mg/kg bw/d azelaic acid, and a control group of 10 gravid rats was given untreated feed. Half of each group was killed and necropsied on day 19 of gestation, and the remaining animals continued dosing for 3 mos. The day of gestation that dosing started is not clear. No gross or microscopic lesi...","page":21,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_008"} |
| CIR_vision_codex |
NOAEL |
=1000 |
mg/kg bw |
rat |
- |
- |
developmental toxicity |
{"citation":"0; 54; 35","dose":"The reproductive toxicity of 0 to 1000 mg/kg bw dodecanedioic acid was evaluated in an OECD com- bined repeated doe and reproductive/developmental toxicity screening test using male and female Crl:CD:BR rats.54 The no-observable effect level (NOEL) for reproductive and devel- opmental toxicity was 1000 mg/kg bw.","effect":"sing started is not clear. No gross or microscopic lesions were observed for the uteri, pla- centas, or ovaries. There were no differences in reproductive or developmental effects between treated and control groups, nor were there any differences in fetal weights of the live fetuses. Dodecanedioic Acid. The reproductive toxicity of 0 to 1000 mg/kg bw dodecanedioic acid was evaluated in an OECD com- bined repeated doe and reproductive/developmental toxicity screening test using male and female Crl:CD:BR rats.54 The no-observable effect level (NOEL) for reproductive and devel- opmental toxicity was 1000 mg/kg bw. Sodium Salt of Adipic, Azelaic, Sebacic, and Dodecanedioic Acids. The influence of the sodium salt of some dicarboxylic acids (adipic acid, azelaic acid, sebacic acid, dodecanedioic acid) on both spontaneous and evoked muscle activity of the uterine horns of 35 female Wistar rats (250-300 g) has been studied in vitro.68 Spontaneous activity of uterine muscle was inhibited by dicarboxylic salts causing the total abolition of mechanical events at concentrations of 24, 32, 40,...","page":21,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_009"} |
| CIR_vision_codex |
NOAEL |
=200 |
mg/kg bw |
rat |
- |
4 weeks |
NOAEL study |
{"citation":"200; 4","dose":"In the ovary, an increase in atresia of the large follicle and a decrease in currently formed corpora lutea were seen in animals dosed with 1000 and 2000 mg/kg bw, and in the 2000 mg/kg bw group, an increase in follicular cysts was observed.","effect":"and a statistically significant decrease in the relative weight of the left ovary. Microscopi- cally, abnormal findings were reported for both the ovary and kidney. In the ovary, an increase in atresia of the large follicle and a decrease in currently formed corpora lutea were seen in animals dosed with 1000 and 2000 mg/kg bw, and in the 2000 mg/kg bw group, an increase in follicular cysts was observed. In the kidney, an eosinophilic change of the proximal tubule was observed for the 2000 mg/kg bw dose group. The NOAEL was 200 mg/kg bw. In the rats dosed for 4 weeks, similar observations were made. There was staining around the perineum of animals dosed with 1000 and 2000 mg/kg bw diethylhexyl adipate, and final bws of animals dosed with 2000 mg/kg bw were statisti- cally significantly decreased. The relative kidney to bws were statistically significantly increased in animals at all dose levels, and liver weights were statistically significantly increased in animals of the 1000 and 2000 mg/kg bw dose groups. The mean estrous cycle length was statistically significantly decreased i...","page":41,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_010"} |
| CIR_vision_codex |
NOAEL |
=610 |
mg/kg bw |
rat |
oral |
90-day |
repeated dose toxicity |
{"citation":"2; 90; 10","dose":"With the excep- tion of decreased weight gain for some of the groups, no compound-related toxicologic effects were observed.2 In a 90-day dietary study, groups of 10 rats per group were fed 0 to 4740 mg/kg bw diethylhexyl adipate for 90 days.113 Mortality occurred in the 4740 mg/kg bw group, but the num- ber of deaths was not specified.","effect":"ethylhexyl adipate. With the excep- tion of decreased weight gain for some of the groups, no compound-related toxicologic effects were observed.2 In a 90-day dietary study, groups of 10 rats per group were fed 0 to 4740 mg/kg bw diethylhexyl adipate for 90 days.113 Mortality occurred in the 4740 mg/kg bw group, but the num- ber of deaths was not specified. Decreased growth and feed consumption was reported for animals fed 2920 mg/kg bw. Changes in kidney and liver weights were noted, but no details were given. The NOEL was 610 mg/kg bw, and the LOEL was 2920 mg/kg bw diethylhexyl adipate. Groups of 15 male and 15 female Sprague Dawley rats were fed 0 or 2.5% diethylhexyl adipate for 90 days.92 At study termination, all animals were killed for necropsy. Body weight gains were statistically significantly decreased for treated males and females, and relative kidney and liver to bws were statistically significantly increased for treated females, when compared to controls. In a 13-week dietary study in which groups of 5 to 8 rats and mice were fed diets containing 0% to 4.0% and 0% to...","page":41,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_011"} |
| CIR_vision_codex |
NOAEL |
<4000 |
mg/kg |
rat |
- |
- |
NOAEL study |
{"citation":"9; 1; 92","dose":"specified 9.1 g/kg 92 Diisooctyl Adipate rats 5/group 2000-64 000 mg/kg, undiluted greater than highest dose tested 92 guinea pigs not specified not specified >5 mL/kg 92 Diisononyl Adipate rats 5/group 346-10 000 mg/kg, undiluted greater than highest dose tested 92 Diisodecyl Adipate NMRI mice 5 male 2000 mg/kg greater than highest dose tested 114 rats n...","effect":"specified 9.1 g/kg 92 Diisooctyl Adipate rats 5/group 2000-64 000 mg/kg, undiluted greater than highest dose tested 92 guinea pigs not specified not specified >5 mL/kg 92 Diisononyl Adipate rats 5/group 346-10 000 mg/kg, undiluted greater than highest dose tested 92 Diisodecyl Adipate NMRI mice 5 male 2000 mg/kg greater than highest dose tested 114 rats not specified undiluted 20 500 mg/kg 92 Dioctyldodecyl Adipate NMRI mice 5 female 2000 mg/kg greater than highest dose tested 115 rats not specified not specified NOAEL <4000 mg/kg 35 Diisocetyl Adipate NMRI mice 5 males 2000 mg/kg greater than highest dose tested 116 Diisopropyl Sebacate NMRI mice 5 female 2000 mg/kg greater than highest dose tested 117 Diethylhexyl Sebacate NMRI mice 5 female 2000 mg/kg greater than highest dose tested 118 mice not specified undiluted 9.5 g/kg 92 (continued) 46S International Journal of Toxicology 31(Supplement 1)","page":42,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_012"} |
| CIR_vision_codex |
NOAEL |
>8000 |
mg/kg |
rat |
dermal |
- |
NOAEL study |
{"citation":"111; 9; 121","dose":"kg 111 Isooctyl Alcohol (metabolite of diisooctyl adipate and diisooctyl sebacate) rats mixture of C7-9 branched alkyl alcohols >2000 mg/kg 121 Nonyl Alcohol (metabolite of diisononyl adipate) rats mixture of C8-10 branched alkyl alcohols 3000 mg/kg 121 Isodecyl Alcohol (metabolite of diisodecyl adipate) rats mixture of C9-11 branched alkyl alcohols 4600...","effect":"kg 111 Isooctyl Alcohol (metabolite of diisooctyl adipate and diisooctyl sebacate) rats mixture of C7-9 branched alkyl alcohols >2000 mg/kg 121 Nonyl Alcohol (metabolite of diisononyl adipate) rats mixture of C8-10 branched alkyl alcohols 3000 mg/kg 121 Isodecyl Alcohol (metabolite of diisodecyl adipate) rats mixture of C9-11 branched alkyl alcohols 4600 mg/kg 121 DERMAL Diethyl Malonate rabbits not specified not specified 16 700 mg/kg 39 Dibutyl Adipate rabbits not specified 96% 20 mL/kg 5 rats not specified i.m. NOAEL >8000 mg/kg 122 Ditridecyl Adipate rabbits 3 2000 mg/kg greater than highest dose tested 92 rabbits 10 5000 m/kg to abraded skin; semi- occlusive greater than highest dose tested 92 Diethylhexyl Adipate rabbits 8 \u00058700 m/kg to abraded skin; occlusive mild irritation; no systemic toxic effects 2 rabbits 1 male/1 female \u00058660 mg/kg for 24 hours, occluded, 1 intact and 1 abraded site >8670 mg/kg 113 Diisononyl Adipate rabbits 4/group 50-3160 mg/kg to abraded skin greater than highest dose tested 92 Diethylhexyl Sebacate guinea pigs not specified not specified <10 000...","page":43,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_013"} |
| CIR_vision_codex |
NOAEL |
=500 |
mg/kg bw/d |
rat |
oral |
13 weeks |
repeated dose toxicity |
{"citation":"10; 0, 50, 150; 500","dose":"Groups of 10 male and 10 female rats were fed 0, 50, 150, or 500 mg/kg bw diisononyl adipate for 13 weeks.92 A statistically significant increase in relative kid- ney to bws was reported for males and females given 500 mg/ kg bw, but absolute kidney weights were not affected and no significant microscopic effects were seen.","effect":"te. Groups of 10 male and 10 female rats were fed 0, 50, 150, or 500 mg/kg bw diisononyl adipate for 13 weeks.92 A statistically significant increase in relative kid- ney to bws was reported for males and females given 500 mg/ kg bw, but absolute kidney weights were not affected and no significant microscopic effects were seen. Microscopic changes in any of the organs, including the testes and epididy- mis of males and ovaries of females, were not observed. There were no significant toxicological findings, and the NOAEL was 500 mg/kg bw/d. In another 13-week study, groups of 4 male and 4 female Beagle dogs were fed 0, 0.3, 1.0, or 3.0% diisononyl adipate; the high dose was increased to 6% during weeks 9 to 13.92 No significant findings were reported for the 0.3 or 1.0% groups. In the high-dose group, decreased bws, testes weight, and feed consumption, increased liver weights, elevated enzyme levels, liver and kidney discoloration, and microscopic changes in the liver, testes, spleen, and kidneys were reported. The dietary NOAEL for diisononyl adipate was 1.0%. Ditridecyl adipate....","page":45,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_014"} |
| CIR_vision_codex |
NOAEL |
=300 |
mg/kg bw |
rat |
- |
- |
developmental toxicity |
{"citation":"100; 300; 5","dose":"In the 100 mg/kg bw group, a statistically significant decrease in the number of live pups was due to an increase in post-implantation loss.","effect":"yl malonate. This effect was not observed in the recovery animals or in the other test groups. No other signifi- cant toxicological effects were observed. Performance in a functional observation battery was similar for test and control animals. There was no effect on fertility. In the 100 mg/kg bw group, a statistically significant decrease in the number of live pups was due to an increase in post-implantation loss. This effect was not considered treatment related, and no develop- mental toxicity was reported. The NOAEL was 300 mg/kg bw for repeated doses and maternal toxicity and 1000 mg/kg bw for fertility and developmental toxicity. Dimethyl Adipate. Groups of 5 gravid Sprague Dawley rats were dosed ip with 0.0603 to 0.6028 mL/kg dimethyl adipate (1/30, 1/10, 1/5, and 1/3 of the ip LD50 value) on days 5, 10, and 15 of gestation.124 A pooled volume control consisted of ani- mals dosed with 10 mL/kg distilled water, saline, or cottonseed oil. A positive control group was not used. All animals were killed and examined on day 20 of gestation. The mean fetal weights and the numbers...","page":53,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_016"} |
| CIR_vision_codex |
NOAEL |
=2000 |
mg/kg bw/d |
rat |
- |
5 days |
developmental toxicity |
{"citation":"0; 3; 16","dose":"Weight gains were statistically sig- nificantly decreased for the 2000 mg/kg bw group during days 0 to 3 and 16 to 20 of gestation.","effect":"imals. No mater- nal mortality was reported. Weight gains were statistically sig- nificantly decreased for the 2000 mg/kg bw group during days 0 to 3 and 16 to 20 of gestation. Weight gains were statistically significantly decreased in the 800 mg/kg bw group during days 0 to 3 of gestation. No differences in skeletal anomalies were observed, but there were some differences in visceral anomalies, including increased incidence of levocardia at 2000 mg/kg bw. These anomalies were not considered treatment-related. The NOAEL for maternal toxicity was 2000 mg/kg bw/d, and for developmental and reproductive effects it was 800 mg/kg bw/d. Groups of 25 mated female rats were dosed dermally with 0 and 2000 mg/kg bw ditridecyl adipate following the same study protocol as above. Again, there were no signs of maternal toxicity. No developmental toxicity was reported, and there were no visceral anomalies or levocardia. Tridecyl adipate, 2000 mg/kg bw, was applied, unoccluded, to groups of 10 male Sprague-Dawley rats, 5 days/week for 13 weeks, and the effect on sperm morphology was evaluated.92...","page":54,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_017"} |
| CIR_vision_codex |
NOAEL |
=170 |
mg/kg bw/d |
- |
oral |
10 weeks |
developmental toxicity |
{"citation":"28, 170; 10; 92","dose":"adipate (calcu- lated as 28, 170, or 1080 mg/kg bw/d) for 10 weeks prior to mating.92 Dosing was terminated, and the animals were mated.","effect":"adipate (calcu- lated as 28, 170, or 1080 mg/kg bw/d) for 10 weeks prior to mating.92 Dosing was terminated, and the animals were mated. (A different source indicated that dosing continued throughout the study).161 A reduction in bw gain was reported during gestation for the dams of the 1.2% group. No test article- related effects on fertility were observed. Fetal weight, total litter weight, and litter size were reduced in the 1.2% group, but the number of pups born live, or their survival, was not affected. The NOAEL was 170 mg/kg bw/d and the LOAEL was 1080 mg/kg bw/d. In another study in which gravid females were fed the same doses as above on days 1 to 22 of gestation, maternal bw and feed consumption were statistically decreased in the 1.2% group. No significant effects on fetal weight or litter size were reported. Animals of the 0.18 and 1.2% groups had slightly increased incidences of minor skeletal abnormalities; this increase was attributed to fetotoxicity. The NOEL for maternal toxicity was 170 mg/kg bw/d. The NOAELs for developmental toxicity and fetotoxicity were 170...","page":55,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_018"} |
| CIR_vision_codex |
NOAEL |
>435 |
mg/kg bw |
rat |
oral |
4 weeks |
oral toxicity |
{"citation":"5; 0; 20","dose":"Groups of 5 rats were dosed with 0 or 3000 mg/kg bw of a neutralized 20% adipic acid solution orally, by gavage, for 4 weeks.49 A nonsignificant decrease in bw gain was observed.","effect":"ropsy at study termination. Groups of 5 rats were dosed with 0 or 3000 mg/kg bw of a neutralized 20% adipic acid solution orally, by gavage, for 4 weeks.49 A nonsignificant decrease in bw gain was observed. In a 4-week study in which a group of 3 rats was dosed orally, by gavage, with 2400 mg/kg bw adipic acid, no significant tox- icological effects were noted. In a 4-week dietary study in which groups of 17 to 20 female rats were fed 0 to 40 mg/d (0-435 mg/kg bw per d) adipic acid, no effects were reported.49 The no-observable adverse effect level (NOAEL) was >435 mg/kg bw per d. In a 5-week dietary study in which groups of 15 to 18 male rats were fed 0 to 800 mg/d (0-13 333 mg/kg bw/d) decreased bw gains, an unkempt appearance, and diarrhea were observed for the animals fed 800 mg/d the first 3 weeks. In another 5-week dietary study in which groups of 4 rats, gender not specified, were fed 100 or 200 mg/d (310-922 mg/kg bw/d) of a 20% adipic acid solution in ethanol, 5 days/week, no signs of toxicity were observed. Ten rats were dosed orally, method not specified, with 199 mg/d...","page":14,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_001"} |
| CIR_vision_codex |
NOAEL |
=3333 |
mg/kg bw |
rat |
oral |
19 weeks |
oral toxicity |
{"citation":"8; 10; 0, 420, 840","dose":"Groups of 8 to 10 male rats were given 0, 420, 840, 1700, or 3400 mg/kg bw/d sodium adipate for 19 weeks in a protein deficient diet.57 Animals were killed after either 7 weeks or at study termination.","effect":"Groups of 8 to 10 male rats were given 0, 420, 840, 1700, or 3400 mg/kg bw/d sodium adipate for 19 weeks in a protein deficient diet.57 Animals were killed after either 7 weeks or at study termination. For unexplained reasons, only 5 to 7 animals/group survived until study termination. Rats of the 3400 mg/kg bw/d group had decreased bw gains and decreased bws. (Statistical significance not stated.) Slight effects were seen in the liver, and the NOAEL was 3333 mg/kg bw. Groups of 13 to 15 male and female rats were fed a diet containing 0, 1600, or 3200 mg/kg bw/d adipic acid for 33 weeks.40 Rats were killed at various intervals throughout the study. Ten of 14 rats fed 3200 mg/kg bw/d died during weeks 0 to 4; surviving rats had decreased weight gains during this time. However, at study termination, bws were for surviving animals of this group were similar to controls. Slight effects were seen in the liver. (Statistical significance not stated.) In a 2-year study, groups of 20 male rats were fed a diet containing 0%, 0.1%, 1%, 3%, and 5% adipic acid (equiv. to 0, 75, 750, 2250, a","page":16,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_002"} |
| CIR_vision_codex |
NOAEL |
=1 |
% |
rat |
oral |
2-year |
inhalation toxicity |
{"citation":"2; 20; 0","dose":"(Statistical significance not stated.) In a 2-year study, groups of 20 male rats were fed a diet containing 0%, 0.1%, 1%, 3%, and 5% adipic acid (equiv. to 0, 75, 750, 2250, and 3750 mg/kg bw/d), and groups of 10 and 19 females were fed 0% and 1% adipic acid, respectively.49 Weight gains of male rats fed 3% and 5% adipic acid were significantly less than...","effect":"imilar to controls. Slight effects were seen in the liver. (Statistical significance not stated.) In a 2-year study, groups of 20 male rats were fed a diet containing 0%, 0.1%, 1%, 3%, and 5% adipic acid (equiv. to 0, 75, 750, 2250, and 3750 mg/kg bw/d), and groups of 10 and 19 females were fed 0% and 1% adipic acid, respectively.49 Weight gains of male rats fed 3% and 5% adipic acid were significantly less than controls. There were no significant tox- icological findings upon gross or microscopic observation. The NOAEL was 1% adipic acid for male and female rats. The effect of adipic acid on hepatic peroxisome prolifera- tion was evaluated in an in vivo study in which 4 male F344 rats were fed chow containing 2% adipic acid dissolved in alcohol.67 After 3 weeks of dosing, the animals were killed. Adipic acid did not induce peroxisome proliferation and did not affect relative liver to bws. Inhalation Mice were exposed to 460 mg/m3 adipic acid dust for 1.5 mos, or to 13 or 129 mg/m3 adipic acid for 4 mos (details not given).40 Decreased weight gain, altered oxidase activity, and up...","page":16,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_003"} |
| CIR_vision_codex |
NOAEL |
=2 |
% |
rat |
oral |
90 days |
repeated dose toxicity |
{"citation":"1; 2; 4","dose":"Groups of 15 male and 15 female rats were dosed orally, by gavage, for 90 days with 0% to 30% of a mixture that contained 4% adipic, 16% glutaric, and 5% succinic acid.55 The vehicle was deionized water, and the dosing volume was 10 mL/kg.","effect":"al chemistry, or urinalysis. There were no microscopic findings or organ weight changes attribu- table to the test substance. There was no treatment-related mortality. The NOAEL was \u00061%, and the LOAEL was 2% glutaric acid. Four male and 4 female Beagle dogs were fed a diet contain- ing 0% to 5% glutaric acid for 90 days.68 Decreased bws, accompanied by reduced feed consumption, were observed for the males and females of the 5% group and females of the 3% group. No other treatment-related effects were observed. The NOAEL was \u00062% and the LOAEL was 3%. Adipic/glutaric/succinic acid mixture. Groups of 15 male and 15 female rats were dosed orally, by gavage, for 90 days with 0% to 30% of a mixture that contained 4% adipic, 16% glutaric, and 5% succinic acid.55 The vehicle was deionized water, and the dosing volume was 10 mL/kg. Two males and 1 female of the 30% group died, and the deaths were considered dose- related. Also in this group, bws were reduced for males and females, and feed consumption was statistically significantly reduced in males. An increased incidence of labored breat...","page":17,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_004"} |
| CIR_vision_codex |
NOAEL |
=3 |
% |
rat |
oral |
180 days |
oral toxicity |
{"citation":"30; 10; 3","dose":"deaths were considered dose- related.","effect":"deaths were considered dose- related. Also in this group, bws were reduced for males and females, and feed consumption was statistically significantly reduced in males. An increased incidence of labored breathing and rales was noted. The urine pH was statistically significantly reduced in both males and females dosed with 30% of the mixture. In the 10% group, bw gains were slightly, but not statistically significantly, reduced in females and feed con- sumption was statistically significantly reduced in males. The NOAEL was 3% and the LOAEL was 10%. Azelaic acid. Groups of 15 male and 15 female Wistar rats were fed a diet containing 140 or 280 mg/kg bw azelaic acid for 180 days, and a control group of 10 males and 10 females was given untreated feed.59 No significant toxicological effects were observed. Growth was similar between test and control groups, as were the microscopic examinations and clinical chemistry parameters. The researchers found similar, negative, results when groups of 10 male and 10 female New Zealand rabbits were fed diets containing 0, 200, or 400 mg/kg bw aze...","page":17,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_005"} |
| CIR_vision_codex |
NOAEL |
=263 |
mg/kg bw |
rat |
oral |
- |
developmental toxicity |
{"citation":"6; 15; 38","dose":"No reproductive, developmental, or maternal effects were observed, and the NOAEL for mater- nal and developmental toxicity was 263 mg/kg bw.","effect":"adipic acid on days 6 to 15 of gestation.38 All animals were killed on day 17 of gestation. No reproductive, developmental, or maternal effects were observed, and the NOAEL for mater- nal and developmental toxicity was 263 mg/kg bw. Similar results were obtained in a study in which gravid Wistar rats were dosed orally, by gavage, with 0, 2.9, 13, 62, or 288 mg/kg bw adipic acid on days 6 to 15 of gestation. The NOAEL for maternal and developmental toxicity was 288 mg/kg bw.38 Groups of 21 to 24 gravid hamsters were dosed orally, by gavage, with 0, 2.9, 5, 44, or 205 mg/kg bw adipic acid on days 6 to 10 of gestation. A significant increase in resorption per implant site was observed with 205 mg/kg bw adipic acid, resulting in a decreased number of live fetuses. (This decrease was not evaluated statisti","page":21,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_006"} |
| CIR_vision_codex |
NOAEL |
=288 |
mg/kg bw |
rat |
oral |
- |
developmental toxicity |
{"citation":"6; 15; 38","dose":"No reproductive, developmental, or maternal effects were observed, and the NOAEL for mater- nal and developmental toxicity was 263 mg/kg bw.","effect":"adipic acid on days 6 to 15 of gestation.38 All animals were killed on day 17 of gestation. No reproductive, developmental, or maternal effects were observed, and the NOAEL for mater- nal and developmental toxicity was 263 mg/kg bw. Similar results were obtained in a study in which gravid Wistar rats were dosed orally, by gavage, with 0, 2.9, 13, 62, or 288 mg/kg bw adipic acid on days 6 to 15 of gestation. The NOAEL for maternal and developmental toxicity was 288 mg/kg bw.38 Groups of 21 to 24 gravid hamsters were dosed orally, by gavage, with 0, 2.9, 5, 44, or 205 mg/kg bw adipic acid on days 6 to 10 of gestation. A significant increase in resorption per implant site was observed with 205 mg/kg bw adipic acid, resulting in a decreased number of live fetuses. (This decrease was not evaluated statistically.) No other effects were reported.38 Groups of 10 to 14 gravid Dutch-belted rabbits were dosed by oral intubation with 0, 2.5, 12, 54, or 250 mg/kg bw adipic acid on days 6 to 18 of gestation. No reproductive, develop- mental, or maternal effe","page":21,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_007"} |
| CIR_vision_codex |
NOAEL |
=250 |
mg/kg bw |
rat |
oral |
- |
developmental toxicity |
{"citation":"4; 205; 6","dose":"4, or 205 mg/kg bw adipic acid on days 6 to 10 of gestation.","effect":"4, or 205 mg/kg bw adipic acid on days 6 to 10 of gestation. A significant increase in resorption per implant site was observed with 205 mg/kg bw adipic acid, resulting in a decreased number of live fetuses. (This decrease was not evaluated statistically.) No other effects were reported.38 Groups of 10 to 14 gravid Dutch-belted rabbits were dosed by oral intubation with 0, 2.5, 12, 54, or 250 mg/kg bw adipic acid on days 6 to 18 of gestation. No reproductive, develop- mental, or maternal effects were observed. The NOAEL for maternal toxicity was \u0006250 mg/kg bw and for developmental toxicity was 250 mg/kg bw.38 Azelaic Acid. Reproductive and teratogenic effects of azelaic acid were evaluated using Wistar rats and New Zealand rab- bits.57 A group of 20 gravid rats was fed a diet containing 140 mg/kg bw/d azelaic acid, and a control group of 10 gravid rats was given untreated feed. Half of each group was killed and necropsied on day 19 of gestation, and the remaining animals continued dosing for 3 mos. The day of gestation that dosing started is not clear. No gross or microscopic lesi...","page":21,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_008"} |
| CIR_vision_codex |
NOAEL |
=1000 |
mg/kg bw |
rat |
- |
- |
developmental toxicity |
{"citation":"0; 54; 35","dose":"The reproductive toxicity of 0 to 1000 mg/kg bw dodecanedioic acid was evaluated in an OECD com- bined repeated doe and reproductive/developmental toxicity screening test using male and female Crl:CD:BR rats.54 The no-observable effect level (NOEL) for reproductive and devel- opmental toxicity was 1000 mg/kg bw.","effect":"sing started is not clear. No gross or microscopic lesions were observed for the uteri, pla- centas, or ovaries. There were no differences in reproductive or developmental effects between treated and control groups, nor were there any differences in fetal weights of the live fetuses. Dodecanedioic Acid. The reproductive toxicity of 0 to 1000 mg/kg bw dodecanedioic acid was evaluated in an OECD com- bined repeated doe and reproductive/developmental toxicity screening test using male and female Crl:CD:BR rats.54 The no-observable effect level (NOEL) for reproductive and devel- opmental toxicity was 1000 mg/kg bw. Sodium Salt of Adipic, Azelaic, Sebacic, and Dodecanedioic Acids. The influence of the sodium salt of some dicarboxylic acids (adipic acid, azelaic acid, sebacic acid, dodecanedioic acid) on both spontaneous and evoked muscle activity of the uterine horns of 35 female Wistar rats (250-300 g) has been studied in vitro.68 Spontaneous activity of uterine muscle was inhibited by dicarboxylic salts causing the total abolition of mechanical events at concentrations of 24, 32, 40,...","page":21,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_009"} |
| CIR_vision_codex |
NOAEL |
=200 |
mg/kg bw |
rat |
- |
4 weeks |
NOAEL study |
{"citation":"200; 4","dose":"In the ovary, an increase in atresia of the large follicle and a decrease in currently formed corpora lutea were seen in animals dosed with 1000 and 2000 mg/kg bw, and in the 2000 mg/kg bw group, an increase in follicular cysts was observed.","effect":"and a statistically significant decrease in the relative weight of the left ovary. Microscopi- cally, abnormal findings were reported for both the ovary and kidney. In the ovary, an increase in atresia of the large follicle and a decrease in currently formed corpora lutea were seen in animals dosed with 1000 and 2000 mg/kg bw, and in the 2000 mg/kg bw group, an increase in follicular cysts was observed. In the kidney, an eosinophilic change of the proximal tubule was observed for the 2000 mg/kg bw dose group. The NOAEL was 200 mg/kg bw. In the rats dosed for 4 weeks, similar observations were made. There was staining around the perineum of animals dosed with 1000 and 2000 mg/kg bw diethylhexyl adipate, and final bws of animals dosed with 2000 mg/kg bw were statisti- cally significantly decreased. The relative kidney to bws were statistically significantly increased in animals at all dose levels, and liver weights were statistically significantly increased in animals of the 1000 and 2000 mg/kg bw dose groups. The mean estrous cycle length was statistically significantly decreased i...","page":41,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_010"} |
| CIR_vision_codex |
NOAEL |
=610 |
mg/kg bw |
rat |
oral |
90-day |
repeated dose toxicity |
{"citation":"2; 90; 10","dose":"With the excep- tion of decreased weight gain for some of the groups, no compound-related toxicologic effects were observed.2 In a 90-day dietary study, groups of 10 rats per group were fed 0 to 4740 mg/kg bw diethylhexyl adipate for 90 days.113 Mortality occurred in the 4740 mg/kg bw group, but the num- ber of deaths was not specified.","effect":"ethylhexyl adipate. With the excep- tion of decreased weight gain for some of the groups, no compound-related toxicologic effects were observed.2 In a 90-day dietary study, groups of 10 rats per group were fed 0 to 4740 mg/kg bw diethylhexyl adipate for 90 days.113 Mortality occurred in the 4740 mg/kg bw group, but the num- ber of deaths was not specified. Decreased growth and feed consumption was reported for animals fed 2920 mg/kg bw. Changes in kidney and liver weights were noted, but no details were given. The NOEL was 610 mg/kg bw, and the LOEL was 2920 mg/kg bw diethylhexyl adipate. Groups of 15 male and 15 female Sprague Dawley rats were fed 0 or 2.5% diethylhexyl adipate for 90 days.92 At study termination, all animals were killed for necropsy. Body weight gains were statistically significantly decreased for treated males and females, and relative kidney and liver to bws were statistically significantly increased for treated females, when compared to controls. In a 13-week dietary study in which groups of 5 to 8 rats and mice were fed diets containing 0% to 4.0% and 0% to...","page":41,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_011"} |
| CIR_vision_codex |
NOAEL |
<4000 |
mg/kg |
rat |
- |
- |
NOAEL study |
{"citation":"9; 1; 92","dose":"specified 9.1 g/kg 92 Diisooctyl Adipate rats 5/group 2000-64 000 mg/kg, undiluted greater than highest dose tested 92 guinea pigs not specified not specified >5 mL/kg 92 Diisononyl Adipate rats 5/group 346-10 000 mg/kg, undiluted greater than highest dose tested 92 Diisodecyl Adipate NMRI mice 5 male 2000 mg/kg greater than highest dose tested 114 rats n...","effect":"specified 9.1 g/kg 92 Diisooctyl Adipate rats 5/group 2000-64 000 mg/kg, undiluted greater than highest dose tested 92 guinea pigs not specified not specified >5 mL/kg 92 Diisononyl Adipate rats 5/group 346-10 000 mg/kg, undiluted greater than highest dose tested 92 Diisodecyl Adipate NMRI mice 5 male 2000 mg/kg greater than highest dose tested 114 rats not specified undiluted 20 500 mg/kg 92 Dioctyldodecyl Adipate NMRI mice 5 female 2000 mg/kg greater than highest dose tested 115 rats not specified not specified NOAEL <4000 mg/kg 35 Diisocetyl Adipate NMRI mice 5 males 2000 mg/kg greater than highest dose tested 116 Diisopropyl Sebacate NMRI mice 5 female 2000 mg/kg greater than highest dose tested 117 Diethylhexyl Sebacate NMRI mice 5 female 2000 mg/kg greater than highest dose tested 118 mice not specified undiluted 9.5 g/kg 92 (continued) 46S International Journal of Toxicology 31(Supplement 1)","page":42,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_012"} |
| CIR_vision_codex |
NOAEL |
>8000 |
mg/kg |
rat |
dermal |
- |
NOAEL study |
{"citation":"111; 9; 121","dose":"kg 111 Isooctyl Alcohol (metabolite of diisooctyl adipate and diisooctyl sebacate) rats mixture of C7-9 branched alkyl alcohols >2000 mg/kg 121 Nonyl Alcohol (metabolite of diisononyl adipate) rats mixture of C8-10 branched alkyl alcohols 3000 mg/kg 121 Isodecyl Alcohol (metabolite of diisodecyl adipate) rats mixture of C9-11 branched alkyl alcohols 4600...","effect":"kg 111 Isooctyl Alcohol (metabolite of diisooctyl adipate and diisooctyl sebacate) rats mixture of C7-9 branched alkyl alcohols >2000 mg/kg 121 Nonyl Alcohol (metabolite of diisononyl adipate) rats mixture of C8-10 branched alkyl alcohols 3000 mg/kg 121 Isodecyl Alcohol (metabolite of diisodecyl adipate) rats mixture of C9-11 branched alkyl alcohols 4600 mg/kg 121 DERMAL Diethyl Malonate rabbits not specified not specified 16 700 mg/kg 39 Dibutyl Adipate rabbits not specified 96% 20 mL/kg 5 rats not specified i.m. NOAEL >8000 mg/kg 122 Ditridecyl Adipate rabbits 3 2000 mg/kg greater than highest dose tested 92 rabbits 10 5000 m/kg to abraded skin; semi- occlusive greater than highest dose tested 92 Diethylhexyl Adipate rabbits 8 \u00058700 m/kg to abraded skin; occlusive mild irritation; no systemic toxic effects 2 rabbits 1 male/1 female \u00058660 mg/kg for 24 hours, occluded, 1 intact and 1 abraded site >8670 mg/kg 113 Diisononyl Adipate rabbits 4/group 50-3160 mg/kg to abraded skin greater than highest dose tested 92 Diethylhexyl Sebacate guinea pigs not specified not specified <10 000...","page":43,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_013"} |
| CIR_vision_codex |
NOAEL |
=500 |
mg/kg bw/d |
rat |
oral |
13 weeks |
repeated dose toxicity |
{"citation":"10; 0, 50, 150; 500","dose":"Groups of 10 male and 10 female rats were fed 0, 50, 150, or 500 mg/kg bw diisononyl adipate for 13 weeks.92 A statistically significant increase in relative kid- ney to bws was reported for males and females given 500 mg/ kg bw, but absolute kidney weights were not affected and no significant microscopic effects were seen.","effect":"te. Groups of 10 male and 10 female rats were fed 0, 50, 150, or 500 mg/kg bw diisononyl adipate for 13 weeks.92 A statistically significant increase in relative kid- ney to bws was reported for males and females given 500 mg/ kg bw, but absolute kidney weights were not affected and no significant microscopic effects were seen. Microscopic changes in any of the organs, including the testes and epididy- mis of males and ovaries of females, were not observed. There were no significant toxicological findings, and the NOAEL was 500 mg/kg bw/d. In another 13-week study, groups of 4 male and 4 female Beagle dogs were fed 0, 0.3, 1.0, or 3.0% diisononyl adipate; the high dose was increased to 6% during weeks 9 to 13.92 No significant findings were reported for the 0.3 or 1.0% groups. In the high-dose group, decreased bws, testes weight, and feed consumption, increased liver weights, elevated enzyme levels, liver and kidney discoloration, and microscopic changes in the liver, testes, spleen, and kidneys were reported. The dietary NOAEL for diisononyl adipate was 1.0%. Ditridecyl adipate....","page":45,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_014"} |
| CIR_vision_codex |
NOAEL |
=300 |
mg/kg bw |
rat |
- |
- |
developmental toxicity |
{"citation":"100; 300; 5","dose":"In the 100 mg/kg bw group, a statistically significant decrease in the number of live pups was due to an increase in post-implantation loss.","effect":"yl malonate. This effect was not observed in the recovery animals or in the other test groups. No other signifi- cant toxicological effects were observed. Performance in a functional observation battery was similar for test and control animals. There was no effect on fertility. In the 100 mg/kg bw group, a statistically significant decrease in the number of live pups was due to an increase in post-implantation loss. This effect was not considered treatment related, and no develop- mental toxicity was reported. The NOAEL was 300 mg/kg bw for repeated doses and maternal toxicity and 1000 mg/kg bw for fertility and developmental toxicity. Dimethyl Adipate. Groups of 5 gravid Sprague Dawley rats were dosed ip with 0.0603 to 0.6028 mL/kg dimethyl adipate (1/30, 1/10, 1/5, and 1/3 of the ip LD50 value) on days 5, 10, and 15 of gestation.124 A pooled volume control consisted of ani- mals dosed with 10 mL/kg distilled water, saline, or cottonseed oil. A positive control group was not used. All animals were killed and examined on day 20 of gestation. The mean fetal weights and the numbers...","page":53,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_016"} |
| CIR_vision_codex |
NOAEL |
=2000 |
mg/kg bw/d |
rat |
- |
5 days |
developmental toxicity |
{"citation":"0; 3; 16","dose":"Weight gains were statistically sig- nificantly decreased for the 2000 mg/kg bw group during days 0 to 3 and 16 to 20 of gestation.","effect":"imals. No mater- nal mortality was reported. Weight gains were statistically sig- nificantly decreased for the 2000 mg/kg bw group during days 0 to 3 and 16 to 20 of gestation. Weight gains were statistically significantly decreased in the 800 mg/kg bw group during days 0 to 3 of gestation. No differences in skeletal anomalies were observed, but there were some differences in visceral anomalies, including increased incidence of levocardia at 2000 mg/kg bw. These anomalies were not considered treatment-related. The NOAEL for maternal toxicity was 2000 mg/kg bw/d, and for developmental and reproductive effects it was 800 mg/kg bw/d. Groups of 25 mated female rats were dosed dermally with 0 and 2000 mg/kg bw ditridecyl adipate following the same study protocol as above. Again, there were no signs of maternal toxicity. No developmental toxicity was reported, and there were no visceral anomalies or levocardia. Tridecyl adipate, 2000 mg/kg bw, was applied, unoccluded, to groups of 10 male Sprague-Dawley rats, 5 days/week for 13 weeks, and the effect on sperm morphology was evaluated.92...","page":54,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_017"} |
| CIR_vision_codex |
NOAEL |
=170 |
mg/kg bw/d |
- |
oral |
10 weeks |
developmental toxicity |
{"citation":"28, 170; 10; 92","dose":"adipate (calcu- lated as 28, 170, or 1080 mg/kg bw/d) for 10 weeks prior to mating.92 Dosing was terminated, and the animals were mated.","effect":"adipate (calcu- lated as 28, 170, or 1080 mg/kg bw/d) for 10 weeks prior to mating.92 Dosing was terminated, and the animals were mated. (A different source indicated that dosing continued throughout the study).161 A reduction in bw gain was reported during gestation for the dams of the 1.2% group. No test article- related effects on fertility were observed. Fetal weight, total litter weight, and litter size were reduced in the 1.2% group, but the number of pups born live, or their survival, was not affected. The NOAEL was 170 mg/kg bw/d and the LOAEL was 1080 mg/kg bw/d. In another study in which gravid females were fed the same doses as above on days 1 to 22 of gestation, maternal bw and feed consumption were statistically decreased in the 1.2% group. No significant effects on fetal weight or litter size were reported. Animals of the 0.18 and 1.2% groups had slightly increased incidences of minor skeletal abnormalities; this increase was attributed to fetotoxicity. The NOEL for maternal toxicity was 170 mg/kg bw/d. The NOAELs for developmental toxicity and fetotoxicity were 170...","page":55,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_018"} |
| CIR_vision_codex |
NOAEL |
>435 |
mg/kg bw |
rat |
oral |
4 weeks |
oral toxicity |
{"citation":"5; 0; 20","dose":"Groups of 5 rats were dosed with 0 or 3000 mg/kg bw of a neutralized 20% adipic acid solution orally, by gavage, for 4 weeks.49 A nonsignificant decrease in bw gain was observed.","effect":"ropsy at study termination. Groups of 5 rats were dosed with 0 or 3000 mg/kg bw of a neutralized 20% adipic acid solution orally, by gavage, for 4 weeks.49 A nonsignificant decrease in bw gain was observed. In a 4-week study in which a group of 3 rats was dosed orally, by gavage, with 2400 mg/kg bw adipic acid, no significant tox- icological effects were noted. In a 4-week dietary study in which groups of 17 to 20 female rats were fed 0 to 40 mg/d (0-435 mg/kg bw per d) adipic acid, no effects were reported.49 The no-observable adverse effect level (NOAEL) was >435 mg/kg bw per d. In a 5-week dietary study in which groups of 15 to 18 male rats were fed 0 to 800 mg/d (0-13 333 mg/kg bw/d) decreased bw gains, an unkempt appearance, and diarrhea were observed for the animals fed 800 mg/d the first 3 weeks. In another 5-week dietary study in which groups of 4 rats, gender not specified, were fed 100 or 200 mg/d (310-922 mg/kg bw/d) of a 20% adipic acid solution in ethanol, 5 days/week, no signs of toxicity were observed. Ten rats were dosed orally, method not specified, with 199 mg/d...","page":14,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_001"} |
| CIR_vision_codex |
NOAEL |
=3333 |
mg/kg bw |
rat |
oral |
19 weeks |
oral toxicity |
{"citation":"8; 10; 0, 420, 840","dose":"Groups of 8 to 10 male rats were given 0, 420, 840, 1700, or 3400 mg/kg bw/d sodium adipate for 19 weeks in a protein deficient diet.57 Animals were killed after either 7 weeks or at study termination.","effect":"Groups of 8 to 10 male rats were given 0, 420, 840, 1700, or 3400 mg/kg bw/d sodium adipate for 19 weeks in a protein deficient diet.57 Animals were killed after either 7 weeks or at study termination. For unexplained reasons, only 5 to 7 animals/group survived until study termination. Rats of the 3400 mg/kg bw/d group had decreased bw gains and decreased bws. (Statistical significance not stated.) Slight effects were seen in the liver, and the NOAEL was 3333 mg/kg bw. Groups of 13 to 15 male and female rats were fed a diet containing 0, 1600, or 3200 mg/kg bw/d adipic acid for 33 weeks.40 Rats were killed at various intervals throughout the study. Ten of 14 rats fed 3200 mg/kg bw/d died during weeks 0 to 4; surviving rats had decreased weight gains during this time. However, at study termination, bws were for surviving animals of this group were similar to controls. Slight effects were seen in the liver. (Statistical significance not stated.) In a 2-year study, groups of 20 male rats were fed a diet containing 0%, 0.1%, 1%, 3%, and 5% adipic acid (equiv. to 0, 75, 750, 2250, a","page":16,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_002"} |
| CIR_vision_codex |
NOAEL |
=1 |
% |
rat |
oral |
2-year |
inhalation toxicity |
{"citation":"2; 20; 0","dose":"(Statistical significance not stated.) In a 2-year study, groups of 20 male rats were fed a diet containing 0%, 0.1%, 1%, 3%, and 5% adipic acid (equiv. to 0, 75, 750, 2250, and 3750 mg/kg bw/d), and groups of 10 and 19 females were fed 0% and 1% adipic acid, respectively.49 Weight gains of male rats fed 3% and 5% adipic acid were significantly less than...","effect":"imilar to controls. Slight effects were seen in the liver. (Statistical significance not stated.) In a 2-year study, groups of 20 male rats were fed a diet containing 0%, 0.1%, 1%, 3%, and 5% adipic acid (equiv. to 0, 75, 750, 2250, and 3750 mg/kg bw/d), and groups of 10 and 19 females were fed 0% and 1% adipic acid, respectively.49 Weight gains of male rats fed 3% and 5% adipic acid were significantly less than controls. There were no significant tox- icological findings upon gross or microscopic observation. The NOAEL was 1% adipic acid for male and female rats. The effect of adipic acid on hepatic peroxisome prolifera- tion was evaluated in an in vivo study in which 4 male F344 rats were fed chow containing 2% adipic acid dissolved in alcohol.67 After 3 weeks of dosing, the animals were killed. Adipic acid did not induce peroxisome proliferation and did not affect relative liver to bws. Inhalation Mice were exposed to 460 mg/m3 adipic acid dust for 1.5 mos, or to 13 or 129 mg/m3 adipic acid for 4 mos (details not given).40 Decreased weight gain, altered oxidase activity, and up...","page":16,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_003"} |
| CIR_vision_codex |
NOAEL |
=2 |
% |
rat |
oral |
90 days |
repeated dose toxicity |
{"citation":"1; 2; 4","dose":"Groups of 15 male and 15 female rats were dosed orally, by gavage, for 90 days with 0% to 30% of a mixture that contained 4% adipic, 16% glutaric, and 5% succinic acid.55 The vehicle was deionized water, and the dosing volume was 10 mL/kg.","effect":"al chemistry, or urinalysis. There were no microscopic findings or organ weight changes attribu- table to the test substance. There was no treatment-related mortality. The NOAEL was \u00061%, and the LOAEL was 2% glutaric acid. Four male and 4 female Beagle dogs were fed a diet contain- ing 0% to 5% glutaric acid for 90 days.68 Decreased bws, accompanied by reduced feed consumption, were observed for the males and females of the 5% group and females of the 3% group. No other treatment-related effects were observed. The NOAEL was \u00062% and the LOAEL was 3%. Adipic/glutaric/succinic acid mixture. Groups of 15 male and 15 female rats were dosed orally, by gavage, for 90 days with 0% to 30% of a mixture that contained 4% adipic, 16% glutaric, and 5% succinic acid.55 The vehicle was deionized water, and the dosing volume was 10 mL/kg. Two males and 1 female of the 30% group died, and the deaths were considered dose- related. Also in this group, bws were reduced for males and females, and feed consumption was statistically significantly reduced in males. An increased incidence of labored breat...","page":17,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_004"} |
| CIR_vision_codex |
NOAEL |
=3 |
% |
rat |
oral |
180 days |
oral toxicity |
{"citation":"30; 10; 3","dose":"deaths were considered dose- related.","effect":"deaths were considered dose- related. Also in this group, bws were reduced for males and females, and feed consumption was statistically significantly reduced in males. An increased incidence of labored breathing and rales was noted. The urine pH was statistically significantly reduced in both males and females dosed with 30% of the mixture. In the 10% group, bw gains were slightly, but not statistically significantly, reduced in females and feed con- sumption was statistically significantly reduced in males. The NOAEL was 3% and the LOAEL was 10%. Azelaic acid. Groups of 15 male and 15 female Wistar rats were fed a diet containing 140 or 280 mg/kg bw azelaic acid for 180 days, and a control group of 10 males and 10 females was given untreated feed.59 No significant toxicological effects were observed. Growth was similar between test and control groups, as were the microscopic examinations and clinical chemistry parameters. The researchers found similar, negative, results when groups of 10 male and 10 female New Zealand rabbits were fed diets containing 0, 200, or 400 mg/kg bw aze...","page":17,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_005"} |
| CIR_vision_codex |
NOAEL |
=263 |
mg/kg bw |
rat |
oral |
- |
developmental toxicity |
{"citation":"6; 15; 38","dose":"No reproductive, developmental, or maternal effects were observed, and the NOAEL for mater- nal and developmental toxicity was 263 mg/kg bw.","effect":"adipic acid on days 6 to 15 of gestation.38 All animals were killed on day 17 of gestation. No reproductive, developmental, or maternal effects were observed, and the NOAEL for mater- nal and developmental toxicity was 263 mg/kg bw. Similar results were obtained in a study in which gravid Wistar rats were dosed orally, by gavage, with 0, 2.9, 13, 62, or 288 mg/kg bw adipic acid on days 6 to 15 of gestation. The NOAEL for maternal and developmental toxicity was 288 mg/kg bw.38 Groups of 21 to 24 gravid hamsters were dosed orally, by gavage, with 0, 2.9, 5, 44, or 205 mg/kg bw adipic acid on days 6 to 10 of gestation. A significant increase in resorption per implant site was observed with 205 mg/kg bw adipic acid, resulting in a decreased number of live fetuses. (This decrease was not evaluated statisti","page":21,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_006"} |
| CIR_vision_codex |
NOAEL |
=288 |
mg/kg bw |
rat |
oral |
- |
developmental toxicity |
{"citation":"6; 15; 38","dose":"No reproductive, developmental, or maternal effects were observed, and the NOAEL for mater- nal and developmental toxicity was 263 mg/kg bw.","effect":"adipic acid on days 6 to 15 of gestation.38 All animals were killed on day 17 of gestation. No reproductive, developmental, or maternal effects were observed, and the NOAEL for mater- nal and developmental toxicity was 263 mg/kg bw. Similar results were obtained in a study in which gravid Wistar rats were dosed orally, by gavage, with 0, 2.9, 13, 62, or 288 mg/kg bw adipic acid on days 6 to 15 of gestation. The NOAEL for maternal and developmental toxicity was 288 mg/kg bw.38 Groups of 21 to 24 gravid hamsters were dosed orally, by gavage, with 0, 2.9, 5, 44, or 205 mg/kg bw adipic acid on days 6 to 10 of gestation. A significant increase in resorption per implant site was observed with 205 mg/kg bw adipic acid, resulting in a decreased number of live fetuses. (This decrease was not evaluated statistically.) No other effects were reported.38 Groups of 10 to 14 gravid Dutch-belted rabbits were dosed by oral intubation with 0, 2.5, 12, 54, or 250 mg/kg bw adipic acid on days 6 to 18 of gestation. No reproductive, develop- mental, or maternal effe","page":21,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_007"} |
| CIR_vision_codex |
NOAEL |
=250 |
mg/kg bw |
rat |
oral |
- |
developmental toxicity |
{"citation":"4; 205; 6","dose":"4, or 205 mg/kg bw adipic acid on days 6 to 10 of gestation.","effect":"4, or 205 mg/kg bw adipic acid on days 6 to 10 of gestation. A significant increase in resorption per implant site was observed with 205 mg/kg bw adipic acid, resulting in a decreased number of live fetuses. (This decrease was not evaluated statistically.) No other effects were reported.38 Groups of 10 to 14 gravid Dutch-belted rabbits were dosed by oral intubation with 0, 2.5, 12, 54, or 250 mg/kg bw adipic acid on days 6 to 18 of gestation. No reproductive, develop- mental, or maternal effects were observed. The NOAEL for maternal toxicity was \u0006250 mg/kg bw and for developmental toxicity was 250 mg/kg bw.38 Azelaic Acid. Reproductive and teratogenic effects of azelaic acid were evaluated using Wistar rats and New Zealand rab- bits.57 A group of 20 gravid rats was fed a diet containing 140 mg/kg bw/d azelaic acid, and a control group of 10 gravid rats was given untreated feed. Half of each group was killed and necropsied on day 19 of gestation, and the remaining animals continued dosing for 3 mos. The day of gestation that dosing started is not clear. No gross or microscopic lesi...","page":21,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_008"} |
| CIR_vision_codex |
NOAEL |
=1000 |
mg/kg bw |
rat |
- |
- |
developmental toxicity |
{"citation":"0; 54; 35","dose":"The reproductive toxicity of 0 to 1000 mg/kg bw dodecanedioic acid was evaluated in an OECD com- bined repeated doe and reproductive/developmental toxicity screening test using male and female Crl:CD:BR rats.54 The no-observable effect level (NOEL) for reproductive and devel- opmental toxicity was 1000 mg/kg bw.","effect":"sing started is not clear. No gross or microscopic lesions were observed for the uteri, pla- centas, or ovaries. There were no differences in reproductive or developmental effects between treated and control groups, nor were there any differences in fetal weights of the live fetuses. Dodecanedioic Acid. The reproductive toxicity of 0 to 1000 mg/kg bw dodecanedioic acid was evaluated in an OECD com- bined repeated doe and reproductive/developmental toxicity screening test using male and female Crl:CD:BR rats.54 The no-observable effect level (NOEL) for reproductive and devel- opmental toxicity was 1000 mg/kg bw. Sodium Salt of Adipic, Azelaic, Sebacic, and Dodecanedioic Acids. The influence of the sodium salt of some dicarboxylic acids (adipic acid, azelaic acid, sebacic acid, dodecanedioic acid) on both spontaneous and evoked muscle activity of the uterine horns of 35 female Wistar rats (250-300 g) has been studied in vitro.68 Spontaneous activity of uterine muscle was inhibited by dicarboxylic salts causing the total abolition of mechanical events at concentrations of 24, 32, 40,...","page":21,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_009"} |
| CIR_vision_codex |
NOAEL |
=200 |
mg/kg bw |
rat |
- |
4 weeks |
NOAEL study |
{"citation":"200; 4","dose":"In the ovary, an increase in atresia of the large follicle and a decrease in currently formed corpora lutea were seen in animals dosed with 1000 and 2000 mg/kg bw, and in the 2000 mg/kg bw group, an increase in follicular cysts was observed.","effect":"and a statistically significant decrease in the relative weight of the left ovary. Microscopi- cally, abnormal findings were reported for both the ovary and kidney. In the ovary, an increase in atresia of the large follicle and a decrease in currently formed corpora lutea were seen in animals dosed with 1000 and 2000 mg/kg bw, and in the 2000 mg/kg bw group, an increase in follicular cysts was observed. In the kidney, an eosinophilic change of the proximal tubule was observed for the 2000 mg/kg bw dose group. The NOAEL was 200 mg/kg bw. In the rats dosed for 4 weeks, similar observations were made. There was staining around the perineum of animals dosed with 1000 and 2000 mg/kg bw diethylhexyl adipate, and final bws of animals dosed with 2000 mg/kg bw were statisti- cally significantly decreased. The relative kidney to bws were statistically significantly increased in animals at all dose levels, and liver weights were statistically significantly increased in animals of the 1000 and 2000 mg/kg bw dose groups. The mean estrous cycle length was statistically significantly decreased i...","page":41,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_010"} |
| CIR_vision_codex |
NOAEL |
=610 |
mg/kg bw |
rat |
oral |
90-day |
repeated dose toxicity |
{"citation":"2; 90; 10","dose":"With the excep- tion of decreased weight gain for some of the groups, no compound-related toxicologic effects were observed.2 In a 90-day dietary study, groups of 10 rats per group were fed 0 to 4740 mg/kg bw diethylhexyl adipate for 90 days.113 Mortality occurred in the 4740 mg/kg bw group, but the num- ber of deaths was not specified.","effect":"ethylhexyl adipate. With the excep- tion of decreased weight gain for some of the groups, no compound-related toxicologic effects were observed.2 In a 90-day dietary study, groups of 10 rats per group were fed 0 to 4740 mg/kg bw diethylhexyl adipate for 90 days.113 Mortality occurred in the 4740 mg/kg bw group, but the num- ber of deaths was not specified. Decreased growth and feed consumption was reported for animals fed 2920 mg/kg bw. Changes in kidney and liver weights were noted, but no details were given. The NOEL was 610 mg/kg bw, and the LOEL was 2920 mg/kg bw diethylhexyl adipate. Groups of 15 male and 15 female Sprague Dawley rats were fed 0 or 2.5% diethylhexyl adipate for 90 days.92 At study termination, all animals were killed for necropsy. Body weight gains were statistically significantly decreased for treated males and females, and relative kidney and liver to bws were statistically significantly increased for treated females, when compared to controls. In a 13-week dietary study in which groups of 5 to 8 rats and mice were fed diets containing 0% to 4.0% and 0% to...","page":41,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_011"} |
| CIR_vision_codex |
NOAEL |
<4000 |
mg/kg |
rat |
- |
- |
NOAEL study |
{"citation":"9; 1; 92","dose":"specified 9.1 g/kg 92 Diisooctyl Adipate rats 5/group 2000-64 000 mg/kg, undiluted greater than highest dose tested 92 guinea pigs not specified not specified >5 mL/kg 92 Diisononyl Adipate rats 5/group 346-10 000 mg/kg, undiluted greater than highest dose tested 92 Diisodecyl Adipate NMRI mice 5 male 2000 mg/kg greater than highest dose tested 114 rats n...","effect":"specified 9.1 g/kg 92 Diisooctyl Adipate rats 5/group 2000-64 000 mg/kg, undiluted greater than highest dose tested 92 guinea pigs not specified not specified >5 mL/kg 92 Diisononyl Adipate rats 5/group 346-10 000 mg/kg, undiluted greater than highest dose tested 92 Diisodecyl Adipate NMRI mice 5 male 2000 mg/kg greater than highest dose tested 114 rats not specified undiluted 20 500 mg/kg 92 Dioctyldodecyl Adipate NMRI mice 5 female 2000 mg/kg greater than highest dose tested 115 rats not specified not specified NOAEL <4000 mg/kg 35 Diisocetyl Adipate NMRI mice 5 males 2000 mg/kg greater than highest dose tested 116 Diisopropyl Sebacate NMRI mice 5 female 2000 mg/kg greater than highest dose tested 117 Diethylhexyl Sebacate NMRI mice 5 female 2000 mg/kg greater than highest dose tested 118 mice not specified undiluted 9.5 g/kg 92 (continued) 46S International Journal of Toxicology 31(Supplement 1)","page":42,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_012"} |
| CIR_vision_codex |
NOAEL |
>8000 |
mg/kg |
rat |
dermal |
- |
NOAEL study |
{"citation":"111; 9; 121","dose":"kg 111 Isooctyl Alcohol (metabolite of diisooctyl adipate and diisooctyl sebacate) rats mixture of C7-9 branched alkyl alcohols >2000 mg/kg 121 Nonyl Alcohol (metabolite of diisononyl adipate) rats mixture of C8-10 branched alkyl alcohols 3000 mg/kg 121 Isodecyl Alcohol (metabolite of diisodecyl adipate) rats mixture of C9-11 branched alkyl alcohols 4600...","effect":"kg 111 Isooctyl Alcohol (metabolite of diisooctyl adipate and diisooctyl sebacate) rats mixture of C7-9 branched alkyl alcohols >2000 mg/kg 121 Nonyl Alcohol (metabolite of diisononyl adipate) rats mixture of C8-10 branched alkyl alcohols 3000 mg/kg 121 Isodecyl Alcohol (metabolite of diisodecyl adipate) rats mixture of C9-11 branched alkyl alcohols 4600 mg/kg 121 DERMAL Diethyl Malonate rabbits not specified not specified 16 700 mg/kg 39 Dibutyl Adipate rabbits not specified 96% 20 mL/kg 5 rats not specified i.m. NOAEL >8000 mg/kg 122 Ditridecyl Adipate rabbits 3 2000 mg/kg greater than highest dose tested 92 rabbits 10 5000 m/kg to abraded skin; semi- occlusive greater than highest dose tested 92 Diethylhexyl Adipate rabbits 8 \u00058700 m/kg to abraded skin; occlusive mild irritation; no systemic toxic effects 2 rabbits 1 male/1 female \u00058660 mg/kg for 24 hours, occluded, 1 intact and 1 abraded site >8670 mg/kg 113 Diisononyl Adipate rabbits 4/group 50-3160 mg/kg to abraded skin greater than highest dose tested 92 Diethylhexyl Sebacate guinea pigs not specified not specified <10 000...","page":43,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_013"} |
| CIR_vision_codex |
NOAEL |
=500 |
mg/kg bw/d |
rat |
oral |
13 weeks |
repeated dose toxicity |
{"citation":"10; 0, 50, 150; 500","dose":"Groups of 10 male and 10 female rats were fed 0, 50, 150, or 500 mg/kg bw diisononyl adipate for 13 weeks.92 A statistically significant increase in relative kid- ney to bws was reported for males and females given 500 mg/ kg bw, but absolute kidney weights were not affected and no significant microscopic effects were seen.","effect":"te. Groups of 10 male and 10 female rats were fed 0, 50, 150, or 500 mg/kg bw diisononyl adipate for 13 weeks.92 A statistically significant increase in relative kid- ney to bws was reported for males and females given 500 mg/ kg bw, but absolute kidney weights were not affected and no significant microscopic effects were seen. Microscopic changes in any of the organs, including the testes and epididy- mis of males and ovaries of females, were not observed. There were no significant toxicological findings, and the NOAEL was 500 mg/kg bw/d. In another 13-week study, groups of 4 male and 4 female Beagle dogs were fed 0, 0.3, 1.0, or 3.0% diisononyl adipate; the high dose was increased to 6% during weeks 9 to 13.92 No significant findings were reported for the 0.3 or 1.0% groups. In the high-dose group, decreased bws, testes weight, and feed consumption, increased liver weights, elevated enzyme levels, liver and kidney discoloration, and microscopic changes in the liver, testes, spleen, and kidneys were reported. The dietary NOAEL for diisononyl adipate was 1.0%. Ditridecyl adipate....","page":45,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_014"} |
| CIR_vision_codex |
NOAEL |
=300 |
mg/kg bw |
rat |
- |
- |
developmental toxicity |
{"citation":"100; 300; 5","dose":"In the 100 mg/kg bw group, a statistically significant decrease in the number of live pups was due to an increase in post-implantation loss.","effect":"yl malonate. This effect was not observed in the recovery animals or in the other test groups. No other signifi- cant toxicological effects were observed. Performance in a functional observation battery was similar for test and control animals. There was no effect on fertility. In the 100 mg/kg bw group, a statistically significant decrease in the number of live pups was due to an increase in post-implantation loss. This effect was not considered treatment related, and no develop- mental toxicity was reported. The NOAEL was 300 mg/kg bw for repeated doses and maternal toxicity and 1000 mg/kg bw for fertility and developmental toxicity. Dimethyl Adipate. Groups of 5 gravid Sprague Dawley rats were dosed ip with 0.0603 to 0.6028 mL/kg dimethyl adipate (1/30, 1/10, 1/5, and 1/3 of the ip LD50 value) on days 5, 10, and 15 of gestation.124 A pooled volume control consisted of ani- mals dosed with 10 mL/kg distilled water, saline, or cottonseed oil. A positive control group was not used. All animals were killed and examined on day 20 of gestation. The mean fetal weights and the numbers...","page":53,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_016"} |
| CIR_vision_codex |
NOAEL |
=2000 |
mg/kg bw/d |
rat |
- |
5 days |
developmental toxicity |
{"citation":"0; 3; 16","dose":"Weight gains were statistically sig- nificantly decreased for the 2000 mg/kg bw group during days 0 to 3 and 16 to 20 of gestation.","effect":"imals. No mater- nal mortality was reported. Weight gains were statistically sig- nificantly decreased for the 2000 mg/kg bw group during days 0 to 3 and 16 to 20 of gestation. Weight gains were statistically significantly decreased in the 800 mg/kg bw group during days 0 to 3 of gestation. No differences in skeletal anomalies were observed, but there were some differences in visceral anomalies, including increased incidence of levocardia at 2000 mg/kg bw. These anomalies were not considered treatment-related. The NOAEL for maternal toxicity was 2000 mg/kg bw/d, and for developmental and reproductive effects it was 800 mg/kg bw/d. Groups of 25 mated female rats were dosed dermally with 0 and 2000 mg/kg bw ditridecyl adipate following the same study protocol as above. Again, there were no signs of maternal toxicity. No developmental toxicity was reported, and there were no visceral anomalies or levocardia. Tridecyl adipate, 2000 mg/kg bw, was applied, unoccluded, to groups of 10 male Sprague-Dawley rats, 5 days/week for 13 weeks, and the effect on sperm morphology was evaluated.92...","page":54,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_017"} |
| CIR_vision_codex |
NOAEL |
=170 |
mg/kg bw/d |
- |
oral |
10 weeks |
developmental toxicity |
{"citation":"28, 170; 10; 92","dose":"adipate (calcu- lated as 28, 170, or 1080 mg/kg bw/d) for 10 weeks prior to mating.92 Dosing was terminated, and the animals were mated.","effect":"adipate (calcu- lated as 28, 170, or 1080 mg/kg bw/d) for 10 weeks prior to mating.92 Dosing was terminated, and the animals were mated. (A different source indicated that dosing continued throughout the study).161 A reduction in bw gain was reported during gestation for the dams of the 1.2% group. No test article- related effects on fertility were observed. Fetal weight, total litter weight, and litter size were reduced in the 1.2% group, but the number of pups born live, or their survival, was not affected. The NOAEL was 170 mg/kg bw/d and the LOAEL was 1080 mg/kg bw/d. In another study in which gravid females were fed the same doses as above on days 1 to 22 of gestation, maternal bw and feed consumption were statistically decreased in the 1.2% group. No significant effects on fetal weight or litter size were reported. Animals of the 0.18 and 1.2% groups had slightly increased incidences of minor skeletal abnormalities; this increase was attributed to fetotoxicity. The NOEL for maternal toxicity was 170 mg/kg bw/d. The NOAELs for developmental toxicity and fetotoxicity were 170...","page":55,"pdf":"PRS528.pdf","row_type":"noael_study","study_id":"PRS528_noael_018"} |