Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The oral LD50 of the test substance was considered to be >2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 28 July, 1993 to 11 August, 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Adopted February 24, 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
December, 1992
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
TEerasil Yellow GWL crude moist (FAT 36'014/F)
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd. Wolferstrasse 4, CH-4414 Fullinsdorf, Switzerland
- Age at study initiation: Approx. 10 weeks
- Weight at study initiation: Males : 231 - 268 g; Females: 168 - 192 g
- Fasting period before study: 16 to 22 h (access to water was not interrupted). Food was presented approx. 3 to 4 h after dosing
- Housing: Group housing of 5 animals/sex/cage in labelled polycarbonate cages containing purified sawdust as bedding material (Woody SPF, supplied by B.M.I., Helmond, The Netherlands)
- Diet: Standard pelleted laboratory animal diet (Kliba 343 from Klingentalmühle Ag, Kaiseraugst, Switzerland) (free access, except for overnight fasting period)
- Water: Tap-water (Free access)
- Acclimation period: At least one week
- Identification: By individual earmark.
- Randomisation: Randomly selected at time of delivery in groups of five.

ENVIRONMENTAL CONDITIONS
- Temperature: 21 °C
- Humidity: 55 %
- Air changes: 15 air changes/h
- Photoperiod: 12 h/12 h (music during light period)
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
1%
Details on oral exposure:
Test substance preparation:
The test substance was placed into a glass beaker on a tared Mettler analytical balance and carboxymethyl cellulose 1 % was added. A weight/weight suspension was prepared using a magnetic stirrer, a mechanical stirrer and an electric blender. The preparation was made immediately prior to each dosing.
Dose volume: 10 mL/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5/sex/dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 15 d
Other examinations performed: clinical signs, body weight,
- Mortality / Viability: At least three times each Day.
- Body Weights: Test Days 1 (pre-administration), 8 and 15
- Clinical Signs: Each animal was examined for changes to treatment with particular attention paid to changes in behaviour, respiration, motility, body posture, motor susceptibility, skin, eyes, nose and fur. Observations were performed four times during Day 1, and once daily during Days 2 - 15. All abnormalities were recorded.
- Necropsy of survivors performed: yes; all animals were necropsied. All animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide asphyxiation.
Statistics:
No data
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 814 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortality occurred during the study period.
Clinical signs:
No clinical signs of ill health or behavioural changes were observed during the study period.
Body weight:
Normal body weight gain was noted in all females over the first week of the study and in all males over the whole study period. However, slightly reduced body weight gain was noted in all females over the second week of the study period compared to Week 1.
Gross pathology:
Macroscopic post mortem examination of the animals at termination did not reveal any significant abnormalities. Renal pelvic dilation, observed in 1/10 treated animals, is a common finding in animals of this age and strain and therefore considered of no toxicological significance.
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 of the test substance was found to be >2000 mg/kg bw (i.e. ca. >1814 mg a.i./kg bw) in rats.
Executive summary:

A study was conducted to assess the acute oral toxicity of the test substance (of 90.7 % purity) in Wistar rats according to OECD Guideline 401 and EU Method B.1 in compliance with GLP. A group of 5 female and 5 male rats received a single oral (gavage) dose of 2000 mg/kg bw of test substance. Parameters assessed included mortality, clinical observations, body weight and necropsy findings in all animals over a 15 d observation period. No mortality and no clinical signs were observed and no significant macroscopic abnormalities were seen at necropsy except renal pelvic dilation, observed in a single male, which is a common finding in animals of this age and strain and was therefore considered to be of no toxicological significance. Further, normal body weight gain was noted in all females over the first week. However, slightly reduced body weight gain was observed among females over Week 2 compared to Week 1. Taking the above findings into account, the oral LD50 of the test substance was >2000 mg/kg bw (i.e. ca. >1814 mg a.i./kg bw) in rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Good Quality Study

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral:

In the key study conducted in Wistar rats according to OECD Guideline 401 and EU Method B., no mortality or clinical signs were seen when FAT 36014/F was administered to a group of rats containing 5 males and 5 females at 2000 mg/kg bw via gavage. Hence, the oral LD50 of the test substance was found to be considered to be >2000 mg/kg bw (i.e. ca. >1814 mg a.i./kg bw) in rats. A few mores single dose studies with oral gavage of test substance FAT 36014 at doses up to 15000 mg/kg bw are available. These studies showed that FAT 36014 has a very low toxicity with an oral LD50 >15000 mg/kg bw.


Inhalation:

Currently no study to assess the acute inhalation toxicity potential of Disperse Yellow 042 is available. However, the vapour pressure for the substance can be considered low owing to the high melting point (>308 °C). Hence the substance is considered to have low volatility. Based on column 2, ‘Specific rules for adaptation from column 1’ of the table given in REACH Annex VII, the study on acute inhalation toxicity only needs to be conducted if an exposure via inhalation is to be expected, based on vapour pressure and/or the likelihood of an exposure to aerosols, particles or droplets. Referring to the expected low volatility of the substance, the fact that the substance is imported into the EU in a formulated form as a dust-free powder or as a granulate, the exposure via inhalation is considered to be unlikely. Further, the chemical was found to have low acute toxicity when tested via oral route with no mortality when tested up to 5000 mg/kg bw. Hence, considering all the above arguments, it is considered that Disperse Yellow 042 has a low toxicity potential via inhalation route and thus the study on acute inhalation toxicity is considered scientifically not necessary.


Dermal:

Currently no study to assess acute dermal toxicity of Disperse Yellow 042 is available. However, the molecular weight of the chemical is 369.4 g/mol, indicating it being large for dermal absorption. Hence, the dermal uptake for the chemical is expected to be limited. The chemical showed low toxicity potential in the available acute oral toxicity studies (LD50 >5000 mg/kg bw), with no mortality or systemic toxicity being seen upto 2000 mg/kg bw, hence it does not need to be classified STOT SE. Similarly, absence of systemic toxicity in skin irritation as well as sensitization studies, further supports the conclusion that no adverse effects are expected for the chemical via the dermal route. Further, experience with similar chemical substances has demonstrated that it is very unlikely that toxicity related to the intrinsic properties of the chemical only show up upon dermal exposure and not after systemic application. Hence, low toxicity is expected on acute dermal exposure of Disperse Yellow 042 and testing by the dermal route was considered scientifically not necessary.

Justification for classification or non-classification

Low toxicity was seen in the acute oral toxicity studies with Disperse Yellow 042 with LD50 being >2000 mg/kg bw, hence the substance does not warrant classification for acute toxicity as per the criteria of Regulation (EC) No. 1272/2008.