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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because it was GLP compliant and although it did not follow any specific guideline it was well documented and an acceptable screening study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Female rats were administered test compound beginning 7 days prior to mating and continued through mating to gestational day 20. Dams were examined for general health and toxicity. Pups were examined for gross abnormalities at birth and body weights recorded on day 0 and 4. Pups were also sexed and observed for survival through day 4.
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Reference substance name:
64741-43-1
Cas Number:
64741-43-1
IUPAC Name:
64741-43-1
Constituent 2
Reference substance name:
VDF gas oil
IUPAC Name:
VDF gas oil
Test material form:
other: liquid
Details on test material:
brown to black-coloured viscous liquid; slightly cracked or burnt to asphaltic odour
Specific Gravity: 0.89- 0.95
Flash Point 150°F

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female

Administration / exposure

Route of administration:
dermal
Vehicle:
unchanged (no vehicle)
Duration of treatment / exposure:
Seven days prior to mating through to gestational day 20
Frequency of treatment:
Once daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0 (sham control), 1, 259 or 1036 mg/kg body weight/day
Basis:
nominal conc.
No. of animals per sex per dose:
15 dams/dose for test groups, 20 dams in untreated control group
Control animals:
yes
Positive control:
No

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
effects observed, treatment-related
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:
not examined
Histopathological findings: non-neoplastic:
not examined
Other effects:
not examined

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
effects observed, treatment-related

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
1 mg/kg bw/day
Sex:
female
Basis for effect level:
other: vaginal discharge, body weight, body weight gain, food consumption, dermal irritation

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings:
not examined

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
1 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: reduced pup weight

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Based on these results, the authors of the study determined a NOAEL of 1 mg/kg body weight/day for effects of VDF gas oil on foetal/pup development (reduced body weight of live pups/ litter and the number of live pups) and maternal toxicity.
Executive summary:

Groups of female Sprague-Dawley rats received 0 (sham control), 1, 259 or 1036 mg/kg body weight/day of VDF gas oil dermally. Treatment of the females commenced one week prior to mating with untreated males. Pregnant females were then assigned to the test (n = 15/dose level) and control groups (n = 20) and treatment continued until gestation day (GD) 20.

None of the dams died during the course of the study. Dermal irritation was present at the treatment site in the mid- and high-dose groups. Mean body weight, weight gain, and food consumption were also reduced in these groups. None of the high-dose females delivered live pups and there was a significant decrease in the number of live pups on lactation day 0. Mean pup weight was significantly reduced at birth and at lactation day 4 for the mid-dose litters, no toxicologically relevant effects were reported for the offspring. Based on these results, the authors of the study determined a NOAEL of 1 mg/kg body weight/day for effects of VDF gas oil on foetal/pup development (reduced body weight of live pups/ litter and the number of live pups) and maternal toxicity.

This study received a Klimisch score of 2 and is classified as reliable with restrictions because it was GLP compliant and although it did not follow any specific guideline it was well documented and an acceptable screening study.