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Description of key information

Oral LD50 in rats > 5000 mg/kg body weight.
Dermal LD50 value > 2000 mg/kg body weight.

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:
5.3.80 - 19.3.80
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study. No analytical purity given.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(adopted 1981)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: RAI f. (SPF) (Ra 25)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: imported from Basle
- Age at study initiation: 5-6 weeks
- Average weight at study initiation: 113 g (males), 102 g (females)
- Fasting before study begin: 18 hours
- Housing: single housing
- Diet: A commercial autoclavable pelleted diet (Labsure CRM rat and mouse nuts), ad libitum.
- Water: Water filtered at 0.45 micron, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2 °C
- Photoperiod: 12 hrs dark / 12 hrs light
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5%
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25% (w/v)
- Amount of vehicle: 20 mL/kg bw
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Observations: deaths and clinical symptoms were recorded (at least once daily).
- Necropsy of survivors performed: yes (at the end of the observation period, surviving animals were killed by exsanguination under ether anaesthesia)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality and no clinical signs were observed.
Mortality:
No mortality was observed.
Clinical signs:
No clinical signs were observed.
Gross pathology:
No abnormalities were seen at terminal autopsy.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
The oral LD50 in rats was determined to be greater than 5000 mg/kg body weight.
Executive summary:

In an oral acute toxicity study pre-dating GLP, five rats per sex were dosed with 5000 mg/kg of the test article in 0.5% CMC by gavage. Following a 14 day observation period all animals were sacrificed and a gross necropsy was performed. No mortality and no clinical signs were observed. No abnormalities were seen at terminal autopsy. As a result, the oral LD50 in rats was determined to be greater than 5000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
reliable with restrictions.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
A study via inhalation route is not appropriate because inhalation of the substance by humans is unlikely.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March 2, 1995 - April 4, 1995
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study. No data on purity.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(adopted 1987)
Deviations:
no
GLP compliance:
yes
Remarks:
Short-term Toxicology, CIBA-GEIGY Limited, 4332 Stein / Switzerland
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Tif: RAI f (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Ciba-Geigy Limited, Animal Production, 4332 Stein / Switzerland
- Age at study initiation: young adult
- Weight at study initiation: 218-228 g
- Housing: individual housing in Macrolon cages, type 3
- Diet: NAFAG 890 Tox, NAFAG, Gossau/SG, Switzerland, ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): 15
- Photoperiod: 12 hrs dark / 12 hrs light
Type of coverage:
semiocclusive
Vehicle:
other: 0.5% (w/v) carboxymethylcellulose in 0.1% (w/v) aqueous polysorbate 80
Details on dermal exposure:
TEST SITE
- Area of exposure: an area on the back of the rat of at least 10% of the body surface was shaved with an electric clipper.
- Type of wrap if used: gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing: with lukewarm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 2000 mg/kg bw; 4 mL/kg bw
- Concentration: 500 mg/mL
- Constant volume or concentration used: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 4 ml/kg bw
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Mortality: daily; a.m. and p.m. on working days, a.m. on weekend days
- Clinical signs and symptoms: daily
- Frequency of weighing: immediately before application and on days 7 and 14
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred and no clinical signs were observed.
Mortality:
No mortality occurred.
Clinical signs:
No signs of acute dermal toxicity were observed in this study.
Body weight:
Body weight was not affected by treatment (see details in table 1 "Any other information on results").
Gross pathology:
At necropsy, no deviations from normal morphology were found.

Table 1: Mean body weight of male and female rats at day 0, 7, and 14.

 

Mean body weight (g) ± sd

Day 0 male

222 ± 3.9

Day 0 female

225 ± 2.3

Day 7 male

265 ± 3.5

Day 7 female

234 ± 7.3

Day 14 male

309 ± 10.6

Day 14 female

243 ± 9.3

Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
The dermal LD50 value of the test article in rats was to determined to be greater than 2000 mg/kg body weight.
Executive summary:

The acute dermal toxicity of the test substance was assessed in a GLP-compliant study following OECD guideline 402. The test article was administered to five rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice. No mortality occurred. No signs of acute dermal toxicity were observed in this study. The mean body weight gain during the observation period was within the range expected for rats used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD50 value of the test substance in rats was established to exceed 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
reliable with restrictions

Additional information

Justification for selection of acute toxicity – oral endpoint
Relevant key study for the assessment.
The oral LD50 in rats was determined to be greater than 5000 mg/kg body weight.

Justification for selection of acute toxicity – dermal endpoint
key study. Dermal LD50 value > 2000 mg/kg body weight

Justification for classification or non-classification

According to the criteria of Regulation (EC) No.: 1272/2008, the substance is not classified as acute toxic.

No signal word, hazard pictogram(s) or hazard statement(s) are required.

Also, according to the criteria specified by Directive 67/548/EEC the substance is not classified with regard to acute toxicity. No symbol or risk phrase is required.

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