Naphthalene-1,5-diol

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: only as secondary citation available: guideline study and GLP

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Test material

Test material information

Constituent 1

Reference substance name:

Naphthalene-1,5-diol

EC Number:

201-487-4

EC Name:

Naphthalene-1,5-diol

Cas Number:

83-56-7

Molecular formula:

C10H8O2

IUPAC Name:

naphthalene-1,5-diol

Test material form:

other: solid

Details on test material:

content: 96.8 % (HPLC)
batch: Ro 576

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

no details available

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1% corboxymethylcellulose wtih 0.5 % cremophor in water

Details on exposure:

1,5-Dihydroxynaphthalene was administered to pregnant rats orally by gavage once daily
from day 6 to day 15 post coitum to the four dose groups 0, 20, 60 and 360 mg/kg bw/day.
Each group consisted of 30 rats. Control animals were dosed with the vehicle alone.
Females were sacrificed on day 20 post coitum and the foetuses were removed by
Caesarean section. The examination of the dams and foetuses was performed in accordance
with international recommendations

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no data

Details on mating procedure:

no data

Duration of treatment / exposure:

day 6 to day 15 of gestation

Frequency of treatment:

once daily

Duration of test:

up to day 20 post coitum

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 20, 60 and 360 mg/kg bw/day.
Basis:
actual ingested

No. of animals per sex per dose:

30 pregnant females per dose group

Control animals:

yes, concurrent vehicle

Details on study design:

1,5-Dihydroxynaphthalene was administered to pregnant rats orally by gavage once daily
from day 6 to day 15 post coitum to the four dose groups 0, 20, 60 and 360 mg/kg bw/day.
Each group consisted of 30 rats. Control animals were dosed with the vehicle alone.
Females were sacrificed on day 20 post coitum and the foetuses were removed by
Caesarean section. The examination of the dams and foetuses was performed in accordance
with international recommendations

Examinations

Maternal examinations:

The examination of the dams and foetuses was performed in accordance
with international recommendations

Ovaries and uterine content:

The examination of the dams and foetuses was performed in accordance
with international recommendations

Fetal examinations:

The examination of the dams and foetuses was performed in accordance
with international recommendations

Statistics:

no data

Indices:

no data

Historical control data:

no data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
The dams tolerated the applied dose of up to 360 mg/kg bw without lethality or symptoms of cumulative intoxication.
But , the corrected mean body weight gain of the high dose group was significantly decreased compared to the control animals.
There were no treatment related effects in the gestation data.

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Effect level:

60 mg/kg bw/day (actual dose received)

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEL

Effect level:

360 mg/kg bw/day

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
The examined foetuses showed no treatment related malformations. the skeletal ossification in all groups was considered to be within normal range.
the testsubstance does not reveal embryotoxic or teratogenic potential at dose levels up to 360 mg/kg bw(day

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Under the condition of this test. 1,5-naphthalenediol does not cause developmental toxicity up to and including the highest test dose of 360 mg/kg bw despite maternal toxicity at 360 mg/kg bw/day.

Executive summary:

According to OECD TG 414 1,5-Dihydroxynaphthalene was administered to pregnant rats orally by gavage once daily from day 6 to day 15 post coitum to the four dose groups 0, 20, 60 and 360 mg/kg bw/day. Each group consisted of 30 rats. Control animals were dosed with the vehicle alone. Females were sacrificed on day 20 post coitum and the foetuses were removed by Caesarean section. The examination of the dams and foetuses was performed in accordance with international recommendations. based on significantly decreased body weight gain at the highest test dose the NOAEL of maternal toxicity was considered 60 mg/kg bw/day. The NOAEL of embryo/fetotoxicity and teratogenicity was 360 mg/kg bw/day, the highest applied dose.