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Administrative data

Description of key information

The test article is of low toxicity after single ingestion and virtually non toxic after single skin contact.

Oral: LD50 = 3230 mg/kg bw

Dermal: LD50 = >3000 mg/kg bw (no study available, assessment based on data from a structurally related compound)

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 Aug. 6, 1981 to Sep. 28, 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
-No individual data; justification for choice of vehicle was not provided
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Tif: RAIf (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Raised on the premises (CIBA-GEIGY Limited, Experimental Toxicology Sisseln GU 2.1)
- Age at study initiation: 7 to 8 weeks
- Weight at study initiation: 200-214 g for males and 176-181 g for females
- Fasting period before study: Animals fasted overnight before orally treated
- Housing: Housed in groups of 5 in Macrolon cages (type 3)
- Diet: NAFAG No. 890, NAFAG, Gossau SG, ad libitum
- Water: ad libitum
- Acclimation period: A minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
oral: gavage
Vehicle:
other: polyethylene glycol 400
Details on oral exposure:
VEHICLE:
Polyethyleneglycol 400 (PEG 400), Fluka AG, Buchs, SG
- Amount of vehicle (if gavage): 10 and 20 ml/kg

MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg

DOSAGE PREPARATION:
The test substance was diluted to achieve a concentration suitable for the dose levels selected for this test.
Doses:
1000, 2500 and 5000 mg/kg body weight.
No. of animals per sex per dose:
10 animals per sex per dose.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weights were recorded immediately prior to dosing and at 7 and 14 days. Physical condition and rate of deaths were monitored throughout the whole observation period.
- Necropsy of survivors performed: Yes, all animals were submitted to a necropsy, whenever they died, survivors at the end of the observation period.

Toxicity rating was evaluated according to company standards (see Table 1).
Statistics:
The LD50, including the 95% confidence limits were calculated by the logit model.
Preliminary study:
Not applicable.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 230 mg/kg bw
95% CL:
2 615 - 4 247
Mortality:
For one sex (not further specified), no deaths were reported in the 1,000 and 2,500 mg/kg groups, nine deaths were reported in the 5,000 mg/kg group: 1 animal died 3 hours after treatment; 4 animals died 24 hours after treatment; 3 animals died 2 days after treatment; 1 animal died 3 days after treatment.

In the other sex (not specified), 2 deaths were reported in the 2,500 mg/kg group and 10 deaths were reported in 5,000 mg/kg group (sex not specified). In the 2,500 mg/kg group, 2 animals died 2 days after treatment. In the 5,000 mg/kg group, 1 animal died 3 hours after treatment; 2 animals died 5 hours after treatment; 6 animals died 24 hours after treatment; 1 animal died 2 days after treatment.
Clinical signs:
The surviving animals recovered within 5-9 days.
In the 1,000 mg/kg dose group: slight sedation was observed at 1, 2, 3, 5, and 24 hours; slight dyspnoea was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 8; slight ruffled fur was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 7; slight diarrhoea was observed at 24 hours and at Day 2; slight curved body position was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 4.
In the 2,500 mg/kg dose group: slight sedation was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 3; slight dyspnoea was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 8; slight exophthalmos was observed at Day 2; slight ruffled fur was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 7; slight diarrhoea was observed at 24 hours and at Day 2; slight curved body position was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 5.
In the 5,000 mg/kg dose group: slight sedation was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 3; slight dyspnoea was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 5; slight ruffled fur was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 6; slight diarrhoea was observed at 24 hours; ventral body position was observed at 3, 5, and 24 hours; slight lateral body position was observed at 2, 3, 5, and 24 hours; slight curved body position was observed at 1, 2, 3, 5, and 24 hours and at Days 2 to 4; moderate tremor was observed at 2 hours and slight tremor was observed at 3, 5, and 24 hours; slight convulsions were observed at 24 hours.
These clinical signs are common effects in this type of study.
Body weight:
See Table 2 for body weight changes.
Gross pathology:
No compound related gross organ changes were observed.
Other findings:
Not applicable.

Table 2. Body weights in grams and standard deviation

Dose (mg/kg)

Males

Females

Day 1

Day 7

Day 14

Day 1

Day 7

Day 14

1,000

200 ± 9.1

246 ± 9.9

289 ± 7.6

180 ± 5.3

197 ± 6.7

216 ± 6.6

2,500

214 ± 6.7

252 ± 7.3

290 ± 6.9

176 ± 3.8

200 ± 5.2

219 ± 6.0

5,000

207 ± 6.7

-

-

181 ± 2.9

-

-

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral LD50 of the test item in rats of both sexes observed over a period of 14 days is 3230 (2615-4247) mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
3 230 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
- Size of the treatment area not indicated, no information on body weight gain
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Tif. RAI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ciba-Geigy breeding unit
- Age at study initiation: not indicated
- Weight at study initiation: 180-200 g
- Housing: individually in Macrolon cages (type 2)
- Diet: ad libitum rat food - NAFAG, Gossau SG
- Water: ad libitum
- Acclimation period: minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 55 ± 5
- Air changes (per hr): not indicated
- Photoperiod (hrs dark / hrs light): 10/14
Type of coverage:
occlusive
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
2%
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: not indicated (shaved area 60 cm2)
- Type of wrap if used: occlusive dressing which was fastened around the trunk with an adhesive elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): not indicated
- Concentration (if solution): 50% formulation
Duration of exposure:
24 hours
Doses:
2150 and 3170 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 170 mg/kg bw
Based on:
test mat.
Mortality:
- Number of deaths at each dose: no deaths occurred
- Time of death: not applicable
Clinical signs:
Dyspnoea, exophthalmus, ruffled fur and hunched posture. Animals recovered within 13 days.
Body weight:
Not reported
Gross pathology:
No test substance related gross changes.
Other findings:
SEX-SPECIFIC DIFFERENCES: None
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 was determined to be higher than 3170 mg/kg bw
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
3 170 mg/kg bw

Additional information

Acute oral toxicity

Two reliable studies assessing the acute oral toxicity of the test article are available. In the key study, ten Tif: RAIf (SPF) rats/sex and dose level were treated with the test substance in PEG 400 at dose levels of 1000, 2500 and 5000 mg/kg body weight by gavage (Ciba-Geigy, 1981). Within the observation period of 14 days sedation, dyspnoea, ruffled fur, diarrhoea, and curved body position have been observed, which were reversible within the observation period. Mortalities occurred at the high dose and the mid dose level. At necropsy, no substance-related gross organ changes have been observed. Based on the results of this study, an LD50 of 3230 (2615 -4247) mg/kg bw was derived.

This finding was supported in a second study conducted with groups of five Tif: RAIf (SPF) rats per sex (Ciba-Geigy, 1979). The test article in PEG 400 was administered at dose levels of 100, 200, 3000, 4000, 6000 and 8000 mg/kg body weight. Within the observation period of 14 days sedation, dyspnoea, ruffled fur and curved body position have been observed, which were reversible within the observation period. Mortalities were recorded at dose levels of 3000 mg/kg and higher. No substance related gross organ changes were seen. Based on the results of this study, an LD50 of 3125 (2369-3920) mg/kg bodyweight was determined.

Acute dermal toxicity

No study is available. Assessment is based on a study performed with a structurally related compound (see attached read across justification). In this acute dermal toxicity study, three New Zealand White rabbits per sex were given a single dermal dose of the test substance at dose levels of 2150 and 3170 mg/kg body weight. The test compound was applied occlusively and held in place for 24 hours followed by an observation period of 14 days. No deaths occurred. Based on the results of this study, a dermal LD50 of >3170 mg/kg bw was derived.

Acute inhalation toxicity

No data available

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the present data, classification for acute toxicity is not warranted under Regulation (EC) No.1272/2008.