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Administrative data

Description of key information

Oral LD50 >5000 mg/kg bw (rats, OECD TG 401)

Dermal LD50 >2000 mg/kg bw (rats, OECD TG 402)

Inhalation LC50 >935 mg/L (rabbits, OECD TG 403)

Key value for chemical safety assessment

Acute toxicity: via oral route

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Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09.02.1987 to 03.03.1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Tif RAIf (SPF), Sprague-Dawley derived
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Ciba-Geigy Ltd, Animal Production, Sisseln, Switzerland
- Age at study initiation: 7 - 8 weeks
- Weight at study initiation: 162-212g
- Fasting period before study: Not specified
- Housing: conventional laboratory cages
- Diet (e.g. ad libitum): Not specified
- Water (e.g. ad libitum): Not specified
- Acclimation period: 5 days


IN-LIFE DATES: From: 09.02.1987 To: 03.03.1987
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
The test material was admixed to distilled water containing 0.5% CMC and 0.1% polysorbate 80.
The dosing solution was prepared immediately before administration. The stability was therefore not checked. 10 ml of the solution per kg body weight were applied by gastric intubation. The highest dose group received 20 ml/kg body weight due to the poor solubility of the test material.
Doses:
2000 or 5000 mg/kg bw
No. of animals per sex per dose:
Five per sex per group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: obsrved hourly for 5 h on day of dosing and twice daily subsequently. Bodyweights recorded pre-test and at weekly intervals
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Not applicable - median lethal dose exceeded Guideline limit dose of 2000 mg/kg bw
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
None of the rats dosed at 2000 mg/kg bw died. One of four males dosed at 5000 mg/kg bw died and two of five females at the higher dose level.
Clinical signs:
Dyspnea, exophthalmus, ruffled fur and curved body positions were observed in all animals. Recovery was evident by day 13.
Body weight:
No information
Gross pathology:
No macroscopic abnormalities noted among rats dosed at 2000 mg/kg bw.
Haemorrhagic lungs and stomachs for one male and two females dosed at 5000 mg/kg bw. Intestinal dilation noted for one female
Other findings:
None
Interpretation of results:
not classified
Conclusions:
LD50 greater than 5000 mg/kg bw
Executive summary:

The acute toxicity of the substance to rat was investigated under GLP to OECD TG 401. Groups of Tif RAIf (SPF), Sprague-Dawley derived rats were dosed with cloquintocet-mexyl at doses of 2000 or 5000 mg/kg test material in 0.5% aqueous carboxymethyl cellulose and 0.1% polysorbate 80. The animals were assessed daily for the following 14 days for any signs of systemic toxicity and their bodyweights recorded at intervals throughout the study. After 14 days surviving rats were sacrificed and subjected to gross necropsy as were those rats which died spontaneously. Dyspnea, exophthalmus, ruffled fur and curved body positions were observed in all animals. At 5000 mg/kg bw one male and two females died. Surviving animals recovered within 13 days. At necropsy, no macroscopic abnormalities were found at 2000 mg/kg. At 5000 mg/kg one male and 2 females showed hemorrhagic lungs and a hemorrhagic stomach. The small intestine of one female was dilated. The acute oral LD50 of the substance was greater than 5000 mg/kg in male and female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw
Quality of whole database:
Fully reliable GLP studies on rats and mice are available. The study in the rat was used as key study.

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 March 1987 to 26 May 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Using the available equipment it was not possible to generate an atmosphere with a concentration of greater than 935 ug/m3
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source of animals: Interfauna U.K. Ltd. Abbots Road, Cambridgeshire
- Age at study initiation: 6-8 weeks
- Weight at study initiation: circa 200 g
- Fasting period before study: None specified
- Housing: Conventional laboratory cages
- Diet (e.g. ad libitum): not specified
- Water (e.g. ad libitum): Not specified
- Acclimation period: 5 days

IN-LIFE DATES: From: 12.03.1987 To: 26.05.1987
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: aerosol generated using Wright dust generator
- Exposure chamber volume: not specified
- Method of holding animals in test chamber: nose-only exposure restraint tubes
- Source and rate of air: flow rate for air supply was 25 L/min
- Method of conditioning air: not specified
- System of generating particulates/aerosols: Wright dust generator
- Method of particle size determination: two samples taken duriing exposure using Cascade impactor
- Treatment of exhaust air: not specified
- Temperature, humidity, pressure in air chamber: temperature - 22.0 +/- 0.1C; Humidity 42+/-2% RH

TEST ATMOSPHERE
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): air
- Concentration of test material in vehicle (if applicable): Nominal concentration = 935 mg/m3 and gravimetrically determined concentration = 935+/-482 mg/m3

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: see tabulated results



Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
The maximum possible concentration that could be achieved for this test material under the conditions of the test was 935 mg/m3. From gravimetric analysis it was determined that in excess of 70% of the dust generated was respirable.
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed twice daily for 14 days. Bodyweights recorded pre-test and at weekly intervals subsequently
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, food consumption
Statistics:
No statistical analysis as the median lethal dose concentration exceeded the maximum atmosphere concentration that could be generated.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 935 mg/m³ air
Based on:
other: nominal concentration
Exp. duration:
4 h
Remarks on result:
other: One male only (of five males and five females) died.
Mortality:
One male died immediately after removal from the exposure chamber
Clinical signs:
other: Dyspnoea, lethargy and brown stains around the snout were observed in most treated animals
Body weight:
All animals gained weight during the study
Gross pathology:
The stomach of the rat which died was distended with gas. There were no other macroscopic abnormalities observed
Other findings:
None

Sex

Dose

Mortality

Male

Control group

935 mg/m3

0 / 5

1 / 5

Female

Control group

935 mg/m3

0 / 5

0 / 5

 

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The inhalation LC50 in rats was greater than 935 mg/m3 (the maximum practical atmosphere concentration that could be generated).
Executive summary:

The acute inhalation toxicity of the substance to rats was studied under GLP to OECD TG 403. The substance was administered by inhalation exposure to Wistar rats 6-8 weeks old at study initiation. There were 5 males and 5 females in the treated group and a further group of controls. An atmosphere was generated by a Wright dust generator, which scraped the test material from the surface of a compressed powder in a stream of air (flow rate 25 L/min). The maximum concentration which could be generated was 935 mg/m3. The animals were exposed for 4 hours in a nose-only chamber. Animals were observed twice daily for 14 days following exposure. Body weights and food consumption were recorded pretest and weekly thereafter. After 14 days surviving animals were sacrificed and subjected to gross necropsy. Lung weights were recorded. One male died immediately following completion of the exposure period. The remaining nine rats survived. Clinical observations included dyspnoea, lethargy and brown stains around the snout. All rats gained weight and no necropsy abnormalities were seen. The inhalation LC50 was greater than 935 mg/m3.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating conc.
Value:
935 mg/m³
Quality of whole database:
One fully reliable GLP study on rats is 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
Study period:
17 March 1987 to 31 March 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Tif RAIf rats
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: not specified
- Age at study initiation:7 - 8 weeks
- Weight at study initiation: 210 - 254 g
- Fasting period before study: not applicable
- Housing: not specified
- Acclimation period: not specified

IN-LIFE DATES: From: 17.03.1987 To: 31.03.1987
Type of coverage:
semiocclusive
Vehicle:
other: 0.5% carboxymethylcellulose and 0.1% polysorbate 80 in distilled water
Details on dermal exposure:
The application site was covered with gauze pad which was held in place for 24 hours with a tape
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
- Frequency of observations and weighing: animals weighed at weekly intervals
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, and dermal reactions
Statistics:
No statistical analysis needed. LD50 estimated from limit dose administration
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No effects at limit dose level
Mortality:
No deaths occurred following topical administration of a dose of 2000 mg/kg bw
Clinical signs:
Slight dyspnoea, curved body position and slight sedation were reported. Complete recovery was reported within 12 days after treatment
Body weight:
Bodyweights not reported
Gross pathology:
No macroscopic abnormalities noted during necropsy
Other findings:
Not applicable

The dermal LD50 was found to exceed the limit dose of 2000 mg/kg bw administered in this study.

Interpretation of results:
not classified
Conclusions:
The dermal LD50 for rats determined for both sexes, was greater than 2000 mg/kg bw
Executive summary:

The acute dermal toxicity of the substance was studied under GLP to OECD TG 402. Cloquintocet-mexyl was administered as a suspension in 0.5% carboxymethyl cellulose and 0.1% polysorbate 80 in distilled water, applied to the shaved dorsum of five male and five female Tif RAIf rats at a single dose level of 2000 mg/kg body weight. The application site was covered with gauze pad which was held in place for 24 hours with a tape. The animals were observed for symptoms of toxicity and mortality for 14 days and then subjected to necropsy procedures. No mortality occurred. Clinical signs of reaction to treatment were limited to commonly observed effects including dyspnoea, curved body position and slight sedation. Recovery was complete within 12 days. At necropsy there were no deviations from normal morphology. The dermal LC50 was greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
One fully reliable GLP study on rats is available.

Additional information

The acute oral toxicity of the substance to rats was tested under GLP to OECD TG 401 (Hartmann 1987). Groups of five female and five male rats received a single oral dose of the test substance by gavage at 2000 or 5000 mg/kg bw. Test animals were observed for a period of 14 days after administration. Two females and one male in the groups receiving 5000 mg/kg bw died before the end of the observation period, whereas the remaining animals survived until the scheduled sacrifice. The oral LD50 in rats was determined to be >5000 mg/kg bw. A second study conducted under GLP to OECD TG 401 tested the acute oral toxicity to mice (Hartmann 1987b). Test animals received a single oral dose of 2000 mg/kg bw by gavage and were then observed for a period of 14 days. None of the animals died before scheduled sacrifice and the oral LD50 was thus >2000 mg/kg bw.

The acute inhalation toxicity of the substance to rats was studied under GLP to OECD TG 403 (Jackson 1987). Groups of five female and five male rats were exposed (nose-only) to a dust atmosphere which was produced by a dust generator scraping the test material from the surface of a compressed powder into a stream of clean air. The maximum achievable concentration was 935 mg/m3 in this study, and test animals were exposed to this concentration for a period of 4 hours. Animals were then observed for a period of 14 days. One male rat died immediately after the exposure period, while all remaining animals survived until the scheduled sacrifice. The inhalation LC50 was determined to be >935 mg/m3.

The acute dermal toxicity of the substance to rats was investigated under GLP to OECD TG 402 (Hartmann 1987c). A dose of 2000 mg/kg bw in 0.5% carboxymethylcellulose, 0.1% polysorbate 80 and distilled water was applied to the shaved skin (dorsum) of five male rats and covered with a gauze pad for a period of 24 hours. Animals were then observed for a period of 14 days. None of the animals died during the observation period. The dermal LD50 was >2000 mg/kg bw.

Justification for classification or non-classification

There are sufficient data on cloquintocet-mexyl to indicate that the substance is of low acute toxicity by the oral and dermal routes. One test animal died immediately after the exposure phase in the test on acute inhalation toxicity at the maximum achievable dust concentration. A classification into Acute Tox. Cat. 4 (inhalation) under Regulation (EC) No. 1278/2008 is therefore proposed.