Registration Dossier

Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
≥ 1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 422) but study period and year of publication not clear (≥ 1997) and only summary available in English.
Cross-reference
Reason / purpose:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1997
Reference Type:
secondary source
Title:
SIDS INITIAL ASSESSMENT PROFILE
Author:
SIDS
Year:
2012
Bibliographic source:
CoCAM 2, 17-19 April 2012
Reference Type:
secondary source
Title:
SIDS Initial Assessment Report
Author:
SIDS
Year:
2012
Bibliographic source:
Paris, France, 17th-19th April, 2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): o-sec-butylphenol
- Substance type: Mono-alkylphenol
- Analytical purity: 99.15%

Test animals

Species:
rat
Strain:
other: Crj:CD(IGS)
Remarks:
(SPF)
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Duration of treatment / exposure:
Males, from 14 days before mating to the day before necropsy (42 days in total)
Females, from 14 days prior to mating to day 3 of lactation (49 days in total)
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (actual dose received)
Dose / conc.:
12 mg/kg bw/day (actual dose received)
Dose / conc.:
60 mg/kg bw/day (actual dose received)
Dose / conc.:
300 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
13
Control animals:
yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:
DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes

FOOD CONSUMPTION: Yes
Oestrous cyclicity (parental animals):
Yes

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
No animals died in any group. Salivation after dosing, decrease in activity and incomplete eyelid opening were observed in males and females of the 300 mg/kg group. In addition an ataxic gait was observed in females of the same group. In the 60 mg/kg group, decrease in locomotor activity was observed in a few males early in the administration period.
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No adverse effects were detected in males and females of the 300 mg/kg group.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No adverse effects were detected in males and females of the 300 mg/kg group.
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Description (incidence and severity):
Hematological examination of males revealed no adverse effects.
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
Concentration of total cholesterol was also increased in males given 300 mg/kg.
Urinalysis findings:
not examined
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Non-neoplastic: hypertrophy of the centrilobular hepatocytes in males of the 300 mg/kg group.
Histopathological findings: neoplastic:
not examined

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
300 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reproductive performance

Results: P1 (second parental generation)

Effect levels (P1)

Key result
Effect level:
300
Sex:
male/female
Remarks on result:
not measured/tested

Results: F1 generation

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
300 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
viability

Overall reproductive toxicity

Key result
Reproductive effects observed:
no
Lowest effective dose / conc.:
300 mg/kg bw/day (actual dose received)

Applicant's summary and conclusion

Executive summary:

An OECD combined repeat dose and reproductive/developmental toxicity screening test was performed in rats for o-sec-butylphenol. With regard to repeat dose toxicity, no animals died in any groups. Salivation after dosing, decrease in activity and incomplete eyelid opening were observed in males and females of the 300 mg/kg group. In addition, an ataxic gait was observed in females of the same group. An increase in relative liver weight was observed in males and females, and hypertrophy of the centrilobular hepatocytes in males of the 300 mg/kg group. Concentration of total cholesterol was also increased in males given 300 mg/kg. No adverse effects were detected on food consumption and body weight change in males and females of the 300 mg/kg group. In the 60 mg/kg group, decrease in locomotor activity was observed in a few males early in the administration period. The NOELs for repeat dose toxicity are considered to be 12 mg/kg/day in males and 60 mg/kg/day in females.

 

Regarding reproductive and developmental toxicity, no adverse effects were observed on copulation, fertility, maintenance of pregnancy, delivery, and lactation. In addition, o-sec-butylphenol did not affect the viability of neonates, sex ratio, body weight changes, and morphological appearance of pups. NOELs for reproductive and developmental toxicity are considered to be 300 mg/kg/day in males, females and pups.