Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to OECD guideline 414 in compliance to GLP.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2006
Report date:
2006
Reference Type:
other: Published secondary source
Title:
Unnamed
Year:
2011
Report date:
2011

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Reference substance name:
Reaction mass of [7-hydroxy-8-[(2-methoxyphenyl)azo]-2-naphthyl]trimethylammonium chloride and [7-hydroxy-8-[(2-methoxyphenyl)azo]-2-naphthyl]trimethylammonium methyl sulphate
EC Number:
916-603-5
IUPAC Name:
Reaction mass of [7-hydroxy-8-[(2-methoxyphenyl)azo]-2-naphthyl]trimethylammonium chloride and [7-hydroxy-8-[(2-methoxyphenyl)azo]-2-naphthyl]trimethylammonium methyl sulphate
Details on test material:
Test substance : Basic Red 76 (COLIPA number C008)
Batch number : 12/13B
Methylsulphate anion : 11.4%
Chloride ion : 4.4%
Water : 3.1%
o-Anisidine : 11ppm
Purity : 98.5% (HPLC)

Test animals

Species:
rat
Strain:
Wistar

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Milli-U water
Details on exposure:
Dose levels were based on the results of a range-finding study.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Animals were treated on day 6-20 of gestation
Frequency of treatment:
Animals were treated once daily
Duration of test:
Animals were sacrificed on day 21 of gestation
No. of animals per sex per dose:
Twenty four females per dose group
Control animals:
yes, concurrent vehicle

Examinations

Maternal examinations:
The mortality and the body weight gain were observed daily. Females were checked daily for the presence of clinical signs. Body weights and food consumption of females were determined at periodic intervals. On day 21 all females were subjected to post-mortem examination. External, thoracic and abdominal macroscopic findings were recorded.
Ovaries and uterine content:
The ovaries and uterine horns were dissected and examined for the number of corpora lutea, the weight of the gravid uterus, the number of implantation sites, the number and distribution of live/dead foetuses, the weight of each live foetus and corresponding placenta, foetal sex and externally visible foetal macroscopic abnormalities. Alternate foetuses of each litter were preserved and subjected to skeletal or visceral examinations.

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
60 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
60 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
60 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: reduction in foetal body weight

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

At the low dose group (60 mg/kg bw/day) no maternal, reproductive or developmental toxicity was observed. At the intermediate dose level (250 mg/kg bw/day) maternal toxicity consisted of decreased body weights, body weight gain, for uterus corrected body weight gain and decreased (absolute and relative) food consumption. At the 250 mg/kg bw/day dose level developmental toxicity consisted of decreased foetal body weights and decreased placental weights. At the high dose level (1000 mg/kg bw/day) maternal toxicity consisted of decreased body weights, body weight gain, for uterus corrected body weight gain and decreased (absolute and relative) food consumption. Also at the 1000 mg/kg bw/day there were slight increases in thinning of the central tendon region of the diaphragm and left sided umbilical artery. The incidences of two other visceral observations also showed minimal changes namely an increase in the incidence of foetuses with extension of one or both lobes of the thymus gland into the neck region and absence of foetus with distension of the urinary bladder. A similar but more pronounced atypical ossification pattern (see 250 mg/kg bw/day) was seen. Generally minor changes in thoracic centra slightly above the historical control range are considered to be of no toxicological significance. Based on available data in the study no explanation can be given for the observation that some toxicological findings (maternal body weights and food consumption, foetal body weights, placental weights) were more pronounced at the 250 mg/kg bw/day dose level when compared to the 1000 mg/kg bw/day dose level.

Applicant's summary and conclusion

Conclusions:
The NOAEL for maternal toxicity and developmental toxicity was 60 mg/kg bw/day.

Categories Display