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Effects on fertility

Description of key information

In a One-generation study, with the read across substance DEHA a reproductive NOAEL of 170 mg/kg bw/day was determined.

Effect on fertility: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
170 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Reliability 2
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
2 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Klimisch 4
Additional information

For the reproductive toxicity of diisotridecyl adipate, no study could be located. Information on reproductive toxicity, available for di-2-ethylhexyl adipate as supporting substance, is used for read across.

 Reproductive toxicity of di-2-ethylhexyl adipate was investigated in a One-generation reproduction toxicity study according to OECD TG 415 (Cefic, 1989). In a 28 day repeated dose toxicity study (OECD TG 407), reproductive organs of male and female animals were examined by necropsy and histopathology. In addition spermatogenesis and oestrous cycling was inspected (Miyata, 2006).

In the One-generation study, a reproductive NOAEL of 170 mg/kg bw/day was determined.

The reproductive NOAEL in the repeated dose toxicity study was 200 mg/kg bw/day.

 Di-2-ethyhexyl adipate is a saturated branched chain aliphatic adipate diester and closely related to diisotridecyl adipate. It is used as supporting substances for read across as justified in more detail in the attached read-across-document.

 


Short description of key information:
Studies on fertility using diisotridecyl adipate could not be located. Di-2-ethylhexyl adipate is used as supporting substance for read across.
In a One-generation reproduction toxicity study with di-2-ethylhexal adipate as test substance, a reproduction NOAEL of 170 mg/kg bw/day was determined for the P generation.

Effects on developmental toxicity

Description of key information
Studies on developmental toxicity/teratogenicity with diisotridecyl adipate as test substance could not be located. Di-2-ethylhexyl adipate is used as supporting substance for read across.
In a developmental toxicity study with di-2-ethylhexal adipate, a developmental NOAEL of 170 mg/kg bw/day was determined for rats and a NOAEL of 160 mg/kg bw/day was determined for rabbits.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
170 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Klimisch 2
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
800 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Klimisch 4
Additional information

For the developmental toxicity/teratogenicity of diisotridecyl adipate, no study could be located. Information on developmental toxicity, available for di-2-ethylhexyl adipate as supporting substance, is use for read across.

 

Developmental toxicity of di-2-ethylhexyl adipate (DEHA) was investigated in a prenatal developmental toxicity study according to OECD TG 414 (Cefic, 1988). In this study, a developmental NOAEL of 170 mg/kg bw/day was determined.

Di-2-ethyhexyl adipate is a saturated branched chain aliphatic adipate diester and closely related to diisotridecyl adipate. It is used as supporting substances for read across as justified in more detail in the attached read-across document.

In a study according to GLP and OECD 414 pregnant rabbits were treated with the read across subtance DEHA in the diet at 40, 80 and 160 mg/kg bw/day, which corresponded to 36, 70, and 145mg/kg/day based on the average relative food consumption (BASF, 2014). The mean test article intake was highest at the beginning and exceeded the average value of 145 mg/kg/day until day 18, which is the most sensitive period in fetal development in rabbits. No maternal toxicity was observed in all dose groups. 20 control and 19 litters per treatment group were available for evaluation. There was no difference between treated and control animals with regard to implantation loss, corpora lutea, litter size, sex distribution, fetal body weight, and external and visceral malformations or variations. Doses were based on a preliminary range finding study, in which 5 mated females were exposed to 100, 300, and 1000 mg/kg from days 7 -29 post coitum. Severe toxicity (e.g., body weight loss) was noted after treatment with 300 mg/kg in the diet and via gavage (to exclude palatability problems), so that the maximum dose in the main study was app. one half of 300 mg/kg.

Based on the results in this prenatal developmental toxicity study the maternal and developmental No Observed Adverse Effect Level (NOAEL) was established as being at least 160mg/kg bw/dayin the diet (dose level approximation). Based on the average relative food consumption, this level corresponded to 145 mg/kg bw/day.

Justification for classification or non-classification

The available developmental and one-generation reproduction toxicity data do not warrant classification for developmental toxicity according to EU regulation (Directive 67/548/EEC and Regulation (EC) No. 1272/2008).

Additional information