Pyridine-2-carbaldehyde

Endpoint summary

Description of key information

In rats (female, most sensitive sex), the LD 50 value via oral route is 566 mg/kg bw. The test substance is classified as acute oral toxic cat. 4 (H302).

In rats, the LD50 value via inhalation route is 0.23 mg/L air (female), the test substance is is classified as acute inhaltion toxic , cat 2 (H 330).

In rats, the LD 50 value via dermal route is greater than 2000 mg/kg bw and thus classification is not warranted for acute dermal toxicity.

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:

1983-05-25 to 1983-06-16

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 May 12, 1981

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: outbred WISTARSTOCK , kfm: WIST (SPF Han.)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: males : 7 weeks , females : 8 weeks
- Weight at study initiation: males : 178-216 g , females : 164-190g
- Fasting period before study: 12-18 hours (overnight) before treatment , approximately 1 hour after treatment
- Housing: animals were caged in groups of five in Macrolon cages type 3 with wire mesh lids and standardized granulated soft wood bedding
- Diet (e.g. ad libitum): pelleted standard Kliba 343 , Batch 74/83 and 77/83 rat maintenance diet ad libitum
- Water (e.g. ad libitum): tap water , ad libitum
- Acclimation period: 1 week under test conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

2% solution of CMC in distilled water

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage):
10ml at 400 mg/kg
10ml at 700 mg/kg
10ml at 1000 mg/kg

Doses:

- 400 mg/kg
- 700 mg/kg
- 1000 mg/kg

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:
Mortality : Five times during the first day , daily thereafter
Body weight : Body weights were recorded on the day of administration and days 8 and 15 of the test
Symptoms : Five times at day 1 , daily thereafter for the nature , onset , severity and duration of all gross or visible toxic or pharmacologic effects or time of death
- Necropsy of survivors performed:
yes , all test animals were subjected to a complete gross necropsy . All animals surviving to termination were killed by exsanguination after pentobarbital anestesia . All organ abnormalities were recorded .

- Other examinations performed: other: The animals were checked daily for the symptoms listed below .
General behaviour : aggressive,crying,restlessness/excitement,nervousness,fear,sedation,somnolence,sleep,coma
Respiration : apnea,dyspnea
Eye : chromodacryorrhea,exophthalmos,miosis,mydriasis,whitish discharge,lid adhesion
Nose : rhinorrhea,epistaxis
Motility : akinesia,ataxia,drooped head,hyperkinesia,hypokinesia,paralysis flaccid,paralysis spatic,paddling movements,stiff movements,rolling movements,hunched posture
Body position : ventral body position,latero-abdominal position,curved body position
Skin : erythema,edema,necrosis
Motor susceptibility : spasms,tonic muscle spasms,clonic muscle spasms,opisthotonus,saltatory spasms,trismus,retching,"Straub" phenomenon,tremor,muscle -twitching
Various : loss of weight,emaciation,nagative corneal reflex,diarrhea,ruffled fur,necrosis of tissue of application area,salivation,pallor,cyanosis

Statistics:

The LOGIT Model (COX , Analysis of Binary Data , London 1977) was applied to estimate the LD50 value . Additionally , the 90 , 95 and 99% confidence intervals for the LD50 for each sex and the slope of the concentration response line was estimated .

Sex:

male

Dose descriptor:

LD50

Effect level:

603 mg/kg bw

Based on:

test mat.

95% CL:

>= 407 - <= 773

Sex:

female

Dose descriptor:

LD50

Effect level:

566 mg/kg bw

Based on:

test mat.

95% CL:

>= 359 - <= 728

Sex:

male/female

Dose descriptor:

LD50

Effect level:

585 mg/kg bw

Based on:

test mat.

95% CL:

>= 463 - <= 686

Mortality:

Males :
Dose 400 mg/kg : no animal died
Dose 700 mg/kg : 1 animal died 5 h after application , 3 more animals died 24 h after application
Dose : 1000 mg/kg : 5 animals died 24 h after application

Females :
Dose 400 mg/kg : no animal died
Dose 700 mg/kg : 2 animals died 5 h after application , 3 more animals died 24 h after application
Dose : 1000 mg/kg : 5 animals died 24 h after application

Clinical signs:

other: The following symptoms were observed : 400 mg/kg : sedation,dyspnea,chromodacryorrhea,rhinorrhea,ataxia,curved body position,loss of weight,ruffled fur 700 mg/kg : sedation,dyspnea,ataxia,curved body position,saltatory spasms,loss of weight,ruffled fur,cy

Gross pathology:

Mottled lungs were observed in seven killed rats of the 400 mg/kg group and in 9 rats which died in the 700 mg/kg group . In addition reddened colon was observed in 5 , and mottled liver in 2 rats of the 700 mg/kg group .
All rats of the 1000 mg/kg group showed mottled lungs as well as a reddened and mottled stomach and a reddened colon with red contents .

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The study was performed according to the OECD TG401 without deviations and therefore considered to be of the highest quality (reliability Klimisch 1). The validity criteria of the test system are fulfilled. The test material did induce mortality and treatment-related clinical signs in the dose group of 1000 mg/kg bw (100 % mortality) and in dose group 700 mg/kg bw (90 % mortality). In the dose group 400 mg/kg bw treatment-related clinical signs were observed too (0% mortality). The LD50 was identified to be 585 mg/kg bw for rats of both sexes with a 95% confidence interval of 463 – 686 mg/kg bw.

Executive summary:

The acute oral toxicity of the test material was investigated in rats of both sexes. The test was conducted according to OECD TG401. As doses 400, 700 and 1000 mg/kg bw of the test substance were administered via gavage to the rats. Observations were made for a period of 14 days. The following symptoms were observed :

- 400 mg/kg bw : sedation, dyspnea, chromodacryorrhea, rhinorrhea, ataxia, curved body position, loss of weight, ruffled fur.

- 700 mg/kg bw : sedation, dyspnea, ataxia, curved body position, salutatory spasms, loss of weight, ruffled fur, cyanosis

- 1000 mg/kg bw : crying, ataxia, sedation, dyspnea, ventral-, abdominal and curved body position, spasms, salutatory spasms.

The above symptoms increased in intensity with higher dose levels.

All animals in the highest dose group died within 24 hours. In the 700 mg/kg bw dose group 3 animals died within 5 hours and another 6 within the following 24 hours. No animals died in the lowest dose group. The gross pathology performed after sacrifice reveals the following findings : Mottled lungs were observed in seven killed rats of the 400 mg/kg group and in 9 rats which died in the 700 mg/kg group . In addition reddened colon was observed in 5 , and mottled liver in 2 rats of the 700 mg/kg group . All rats of the 1000 mg/kg group showed mottled lungs as well as a reddened and mottled stomach and a reddened colon with red contents .

An oral LD50 was identified to be 585 mg/kg bw for rats of both sexes with a 95% confidence interval of 463 – 686 mg/kg bw.

LD50 (males) : 603 mg/kg bw with a 95% Confidence interval of 407 - 773 mg/kg bw

LD50 (females) : 566 mg/kg bw with a 95% Confidence interval of 359 - 728 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

566 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001-08-13 to 2001-10-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

The Department of Health of the Government of the United Kingdom

Limit test:

no

Species:

rat

Strain:

other: Sprague-Dawley Crl:CD® (SD) IGS BR strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation : 8 - 12 weeks
- Weight at study initiation : male : 281-324g , female : 221-252g
- Fasting period before study : no
- Housing : The animals were housed in groups of five by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes (Datesand Ltd., Cheshire, UK) and provided with environmental enrichment aids: wooden chew blocks (B & K Universal Ltd, Grimston, Hull,UK) and cardboard “fun tunnels” (Datesand Ltd., Cheshire, UK))
- Diet : Rat and Mouse Expanded Diet No.1 (Special Diets Services Limited, Witham, Essex, UK) , ad libitum with exception of the exposure period
- Water : mains drinking water ,ad libitum with exception of the exposure period
- Acclimation period : at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C) : 21°C , +/-2°C
- Humidity (%) : 55% , +/-15%
- Air changes (per hr) : at least 15
- Photoperiod (hrs dark / hrs light) : 12/12

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: Compressed air , supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus : glass concentric jet nebuliser (Radleys, Saffron Walden, Essex, UK) located at the top of the exposure chamber. The nebuliser was connected to a glass syringe attached to an infusion pump, which provided a continuous supply of test material under pressure, and to a metered compressed air supply.

- Exposure chamber volume : approximately 30l

- Method of holding animals in test chamber : Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber ‘O’ ring .

- Source and rate of air :Compressed air . Chamber air flow rates ranged from 20 to 28 L/min dependent on concentration, providing 40 to 56 air changes per hour .

- Method of conditioning air : Compressed air was supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters.

- System of generating particulates/aerosols : The test material was aerosolised using a glass concentric jet nebuliser (Radleys, Saffron Walden, Essex, UK)

- Method of particle size determination : The particle size of the generated atmosphere inside the exposure chamber was determined three times during each exposure period using a Marple Personal Cascade Impactor (Schaefer Instruments Ltd, Oxon., UK). This device consisted of six impactor stages (9.8, 6.0, 3.5, 1.55, 0.93 and 0.52 µm cut points) with stainless steel collection substrates and a back up glass fibre filter, housed in an aluminium sampler. The sampler was temporarily sealed in a sampling port in the animals’ breathing zone and a suitable, known volume of exposure chamber air was drawn through it using a vacuum pump . The collection substrates and backup filter were weighed before and after sampling and the weight of test material, collected at each stage, calculated by difference

- Treatment of exhaust air : The extract from the exposure chamber passed through a ‘scrubber’ trap and was connected with a high efficiency filter to a metered exhaust system

- Temperature, humidity, pressure in air chamber : The temperature and relative humidity inside the exposure chamber were measured by an electronic thermometer/humidity meter (Hanna Instruments Ltd, Beds., UK) located in a vacant port in the animals’ breathing zone of the chamber and recorded every thirty minutes throughout the four-hour exposure period .The chamber was maintained under negative pressure.

TEST ATMOSPHERE
- Brief description of analytical method used : The actual chamber concentration was measured at regular intervals during each exposure period . The gravimetric method used employed glass fibre filters (Gelman type A/E 25 mm) placed in a filter holder. The holder was temporarily sealed in a vacant port in the exposure chamber in the animals’ breathing zone and a suitable, known volume of exposure chamber air was drawn through the filter using a vacuum pump . Each filter was weighed before and after sampling in order to calculate the weight of collected test material. The difference in the two weights, divided by the volume of atmosphere sampled, gave the actual chamber concentration . The nominal chamber concentration was calculated by dividing the mass of test material used by the total volume of air passed through the chamber.

- Samples taken from breathing zone: yes

VEHICLE
- Concentration of test material in vehicle : mean achieved atmosphere concentrations : 0.74 , 1.89 and 5.23 mg/l


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
- Dose group 1 (Atmosphere concentration : 5.23 mg/l) : MMAD = 1.61 µm ; GSD = 1.51 ; Predicted amount less than 4µm = 98.6%
- Dose group 2 (Atmosphere concentration : 1.89 mg/l) : MMAD = 3.16 µm ; GSD = 1.99 ; Predicted amount less than 4µm = 63.4%
- Dose group 3 (Atmosphere concentration : 0.74 mg/l) : MMAD = 2.30 µm ; GSD = 1.99 ; Predicted amount less than 4µm = 78.8%

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

mean achieved atmosphere concentrations : 0.74 , 1.89 and 5.23 mg/l

No. of animals per sex per dose:

5 males/5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration : 14 days
- Frequency of observations and weighing : All animals were observed for clinical signs at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, one hour after termination of exposure and subsequently once daily for up to fourteen days . Individual bodyweights were recorded prior to treatment on the day of exposure and on Days 7 and 14 or at death
- Necropsy of survivors performed : yes

Statistics:

Using the mortality data obtained, an estimate of the acute inhalation median lethal concentration (LC50) and 95% confidence limits of the test material were calculated using validated toxicity data analysis software (ToxCalc v5.0 (Tidepool Scientific Software, McKinleyville, Ca, USA)). The female and all-animal LC50’s were calculated by the Maximum Likelihood Regression Method (Finney, 1971) whilst the male LC50 was calculated by the Trimmed Spearman-Karber Method (Hamilton et al, 1977).

Sex:

male/female

Dose descriptor:

LC50

Effect level:

0.8 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 95% confidence limit not calculable

Sex:

male

Dose descriptor:

LC50

Effect level:

2.53 mg/L air (analytical)

Based on:

test mat.

95% CL:

>= 1.65 - <= 3.87

Exp. duration:

4 h

Sex:

female

Dose descriptor:

LC50

Effect level:

0.23 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 95% confidence limit not calculable

Mortality:

see Table 1 at "Overall remarks, attachments"

Clinical signs:

other: Signs of hunched posture, pilo-erection and red/brown staining around the snout are commonly seen in animals for short periods on removal from the chamber following 4-hour inhalation studies. Wet fur and fur stained by test material are commonly recorded

Body weight:

One male and two females showed reduced bodyweight development during Week 1 but normal bodyweight development was noted for most surviving animals during the study.

Gross pathology:

With the exception of an isolated instance of dark foci of the lungs, no macroscopic abnormalities were detected amongst surviving animals at terminal kill.
For animals that died or were humanely killed during the course of the study, the following abnormalities were detected:
Lungs – enlarged, pale, abnormally red, abnormally dark;
Liver – dark, accentuated lobular pattern;
Stomach – gaseous distension.

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

The study was performed according to the OECD TG403 without deviations and therefore considered to be of the highest quality (reliability Klimisch 1). The validity criteria of the test system are fulfilled.
The acute inhalation median lethal concentrations (LC50) and 95% confidence limits of Pyridine-2-aldehyde in the Sprague-Dawley Crl:CD® (SD) IGS BR strain rat, were estimated to be:
All animals : 0.80 (non-calculable) mg/l
Males only : 2.53 (1.65 – 3.87) mg/l
Females only : 0.23 (non-calculable) mg/l (230 mg/m3)

An aerosol has been tested and hence, for classification the following criteria for dusts and mists are applicable:
Category 1 LC50 < 0.05 mg/L
Category 2 0.05 mg/L < LC50 = 0.5 mg/L
Category 3 0.5 mg/L < LC50 = 1.0 mg/L
Category 4 1.0 mg/L < LC50 = 5.0 mg/L

Executive summary:

The acute inhalation toxicity of the test material was investigated in rats of both sexes. The test was conducted according to OECD Guidelines for Testing of Chemicals (1981) No. 403 “Acute InhalationToxicity”. Groups of ten Sprague-Dawley Crl:CD® (SD) IGS BR strain rats (five males and five females) were exposed to an aerosol atmosphere. The animals were exposed for four hours using a nose only exposure system, followed by a fourteen day observation period. The mean achieved atmosphere concentrations and the corresponding mortalities were as follows:

Group Number	Atmosphere Concentration		Deaths
	Mean Achieved (mg/L)	Nominal (mg/L)	Male	Female	Total
1	5,23	48,0	5/5	5/5	10/10
2	1,89	17,5	1/5	4/5	5/10
3	0,74	12,0	2/5	4/5	6/10

Clinical Observations: Common abnormalities noted during the study included decreased and/or increased respiratory rate, wet fur, hunched posture and pilo-erection. There were frequent occurrences of laboured respiration, noisy respiration, red/brown staining around the snout and pallor of the extremities and several instances, particularly at the highest concentration, of corneal opacity, severe ataxia, gasping respiration and fur staining by test material. The following observations were seen sporadically: ataxia, coma, cyanosis, hypothermia, lethargy, tremors, clonic convulsions, loss of righting reflex and red/brown staining of the head. One male and two females showed reduced bodyweight development during Week 1 but normal bodyweight development was noted for most surviving animals during the study.

With the exception of an isolated instance of dark foci of the lungs, no macroscopic abnormalities were detected amongst surviving animals at terminal kill.

For animals that died or were humanely killed during the course of the study, the following abnormalities were detected :

Lungs – enlarged, pale, abnormally red, abnormally dark;

Liver – dark, accentuated lobular pattern;

Stomach – gaseous distension.

The acute inhalation median lethal concentrations (LC50) and 95% confidence limits of Pyridine-2-aldehyde in the Sprague-Dawley Crl:CD® (SD) IGS BR strain rat, were estimated to be:

All animals : 0.80 (95% confidence limit non-calculable) mg/L

Males only : 2.53 (95% confidence limit : 1.65 – 3.87) mg/L

Females only : 0.23 (95% confidence limit non-calculable) mg/L 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

230 mg/m³ air

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:

2001-08-16 to 2001-09-03

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

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

(The Department of Health of the Government of the United Kingdom)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Sprague-Dawley CD (Crl: CD® (SD) IGS BR)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation : approximately 8 weeks
- Weight at study initiation : at least 200g
- Fasting period before study : no
- Housing : The animals were housed in suspended polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet : Rat and Mouse SQC Expanded Diet No. 1 (Special Diets Services Limited, Witham, Essex, UK) , ad libitum
- Water : mains drinking water , ad libitum
- Acclimation period : at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C) : 19-25
- Humidity (%) : 30-70
- Air changes (per hr) : at least 15
- Photoperiod (hrs dark / hrs light) : 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure : a shorn area on the back and flank of the rats
- % coverage : 10%
- Type of wrap if used : selfadhesive semi-occlusive bandage

REMOVAL OF TEST SUBSTANCE
- Washing : the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material.
- Time after start of exposure : 24 hours

TEST MATERIAL
- Amount(s) applied : Dose Level : 2000 mg/kg bw (Dose Volume : 1.80 ml/kg)
- Constant volume or concentration used : yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5; initially one male and one female rat were treated with the test material at a dose level of 2000 mg/kg. After evaluation of the reactions in these animals an additional group of four male
and four female animals were treated in a similar manner.

Control animals:

no

Details on study design:

- Duration of observation period following administration : 14 days
- Frequency of observations and weighing : The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days . After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation (according to the DRAIZE scoring system) . Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes

Statistics:

Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: There were no signs of systemic toxicity.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Skin Irritation :
Signs of dermal irritation noted during the study were light brown discolouration of the epidermis, crust formation, small superficial scattered scabs, possible green/brown-coloured dermal necrosis, hardened light brown coloured scab and scab lifting to reveal glossy skin . Adverse reactions prevented evaluation of erythema and oedema at one treated skin site seven to fourteen days after treatment.

Interpretation of results:

GHS criteria not met

Remarks:

according to CLP regulation not classified

Conclusions:

The study was performed according to the OECD TG402 without deviations and therefore considered to be of the highest quality (reliability Klimisch 1).The validity criteria of the test system was fulfilled. The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD (Crl: CD® (SD) IGS BR) strain rat was found to be greater than 2000 mg/kg bodyweight. The test material does not meet the criteria for classification and will not require labelling for dermal toxicity in accordance with the CLP regulation.

Executive summary:

The acute dermal toxicity of the test material was investigated in rats. The test was conducted according to OECD TG402 and EU Method B. 3. 2000 mg/kg bw of the test substance was applied semiocclusive to the shaved skin of rats. After 24 h the animals were unwrapped and observations were made for a period of 14 days. No mortalities occured during the study. There were no signs of systemic toxicity reported. Signs of dermal irritation noted during the study were light brown discolouration of the epidermis, crust formation, small superficial scattered scabs, possible green/brown-coloured dermal necrosis, hardened light brown coloured scab and scab lifting to reveal glossy skin. Adverse reactions prevented evaluation of erythema and oedema at one treated skin site seven to fourteen days after treatment. All animals showed expected gains in bodyweight over the study period except for one male animal which showed bodyweight loss over the second week. No abnormalities were noted at necropsy. The acute dermal median lethal dose (LD50) of the test material, in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. The test material does not meet the criteria for classification and will not require labelling for dermal toxicity in accordance with the CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

In a reliable acute oral toxicity test a LD50 of 585 mg/kg bw for both sexes was determined. Whereby the female animals were the most sensitive with an LD50 of 566 mg/kg bw. For male a LD50 of 603 mg/kg bw was determined.

In a reliable acute inhalation test the females were also the most sensitive with an LD50 of 0.23 mg/l air. For males a LD50 of 2.53 mg/L air and for both sexes a LD50 of 0.8 mg/L air was determined.

In a reliable acute dermal toxicity test a LD50 >2000 mg/kg bw was determined for both sexes.

Justification for classification or non-classification

Based on the available results, the test substance is classified as acute oral toxic cat. 4 (H302) and as acute inhalation toxic cat. 2 (H330) according to Regulation (EC) No 1272/2008. Based on the available results, the test substance is not classified for acute dermal toxicity according to Regulation (EC) No 1272/2008