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Effects on fertility

Description of key information

The adminstration of 12000 ppm (approximately 1080 mg/kg/d) of the read-across substance DEHA in diet led to a reduction in female parent bodyweight gain during pregnancy and a reduction in offspring weight gain and litter size. No other reproductive parameters were affected and, in particular, there were no effects on fertility in either sex. Also were seen increased liver weights at 12000 ppm (approximately 1080 mg/kg/d) in male and female parents. The NOAEL for this study is ca. 170 mg/kg bw/d.

Link to relevant study records
Reference
Endpoint:
one-generation reproductive toxicity
Remarks:
based on test guideline
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please see Analogue Approach
Reason / purpose for cross-reference:
read-across source
Clinical signs:
no effects observed
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
effects observed, treatment-related
Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
TEST SUBSTANCE INTAKE
There was a slight increase in food consumption in males dosed with 12000ppm DEHA from 6-10 weeks of the study, the effect being statistically significant at weeks 6-9. Food utilisation was slifghtly less efficients overall for males receiving 12000ppm DEHA.

ORGAN WEIGHTS
An increase in liver weight was observed for both male and female parents receiving 12000ppm DEHA. No other groupp treatment group was effected. This increase in liver weight has been reported previously and is associated with peroxisome proliferation (Moody and Reddy 1978).
Key result
Dose descriptor:
LOAEL
Effect level:
1 080 mg/kg bw/day (nominal)
Based on:
test mat.
Remarks:
no remarks
Sex:
male/female
Basis for effect level:
other: increased absolute liver weights, and reduced body weight gain in females
Remarks on result:
other: no remarks
Key result
Dose descriptor:
NOAEL
Effect level:
ca. 170 mg/kg bw/day (nominal)
Based on:
test mat.
Remarks:
no remarks
Sex:
male/female
Basis for effect level:
other: increased absolute liver weights, and reduced body weight gain in females
Remarks on result:
other: no remark
Key result
Critical effects observed:
no
Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed
BODY WEIGHT
Mean pup weight gain and total litter weight for both male and female offspring receiving 12000ppm DEHA were reduced throughout the whole of the post partum phase. There was no effect on either male or female pup weight gain in any other dose group in comparison with the control animals.
Key result
Dose descriptor:
LOAEL
Generation:
F1
Effect level:
1 080 mg/kg bw/day (nominal)
Based on:
test mat.
Remarks:
no remarks
Sex:
male/female
Basis for effect level:
other: see 'Remark'
Remarks on result:
other: no remarks
Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
ca. 170 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Mean pup weight gain and total litter weight for both male and female offspring receiving 12000 ppm (1080 mg/kg) DEHA were reduced throughout the whole of the post partum phase (Days 1-36). In addition, mean litter size was slightly reduced at 12000 ppm.
Remarks on result:
other: no remarks
Key result
Reproductive effects observed:
no
Conclusions:
The adminstration of 12000 ppm (approximately 1080 mg/kg/d) of the read-across substance DEHA in diet led to a reduction in female parent bodyweight gain during pregnancy and a reduction in offspring weight gain and litter size. No other reproductive parameters were affected and, in particular, there where no effects on fertility in either sex. Also were seen increased liver weights at 12000 ppm (approximately 1080 mg/kg/d) in male and female parents. The NOAEL for this study is ca. 170 mg/kg bw/d.
Executive summary:

The adminstration of 12000 ppm (approximately 1080 mg/kg/d) of the read-across substance DEHA in diet led to a reduction in female parent bodyweight gain during pregnancy and a reduction in offspring weight gain and litter size. No other reproductive parameters were affected and, in particular, there where no effects on fertility in either sex. Also were seen increased liver weights at 12000 ppm (approximately 1080 mg/kg/d) in male and female parents. The NOAEL for this study is ca. 170 mg/kg bw/d.

It is important additionally to note that for the structure "2 -Ethylhexyl" Reproctiontoxicity is one of the most sensitive endpoints and that these effects are considered as unlikely for the Butanedioic acid, 2,3 -dihydroxy-[R-(R*, R*)]-, C12 -13 -branched alkyl esters. Therefore to mention this study and to take these results is "worst case".

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

For the reproductive toxicity of Butanedioic acid, 2,3 -dihydroxy-[R-(R*,R*)]-, C12 -13 -branched alkyl esters, no study could be located. Information on reproductive toxicity, available for DEHA as supporting substance, is used for read across.

 Reproductive toxicity of DEHA 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.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Justification for classification or non-classification

No classification for reproductive toxicity is indicated according to the classification, labeling and packaging (CLP) regulation (EC 1272/2008).

Additional information

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