Registration Dossier

Administrative data

Description of key information

LD50 Oral (rat) = 1876 mg/kg bw (male) and 1475 mg/kg bw (female)
LD50 Dermal = >2000 mg/kg bw (rat)
LC50 Inhalation-aerosol (rat) = 8.16 mg/l (male/female) with 1 of 10 dead animals at limit dose of approx 5 mg/l.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
Cited as Directive 84/449/EEC, B.1
GLP compliance:
yes
Remarks:
Bayer AG, Institute of Toxicology
Test type:
standard acute method
Specific details on test material used for the study:
- Name of test material (as cited in study report): epsilon-Caprolactam
- Physical state: solid
- Analytical purity: 99.9%
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen
- Age at study initiation: male 9 weeks, female 14 weeks
- Mean weight at study initiation: male 182 g, female 170 g
- Fasting period before study: 16 h before dosing
- Housing: 5 per cage
- Diet (e.g. ad libitum): Altromin 1324 pellets
- Water (e.g. ad libitum): tap water
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 50±10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 ml/kg bw

Doses:
male: 0, 312, 1000, 1250, 1600, 2000, 2250 mg/kg bw
female: 0, 312, 1000, 1250, 1600, 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: several times on the day of application and daily thereafter. Body weights were recorded before application, 7 d post application and at the end of the observation period.
- Necropsy of survivors performed: yes
Statistics:
Rosiello et al., J. Tox. Environ. Health 3, 797, 1977.
Sex:
female
Dose descriptor:
LD50
Effect level:
1 475 mg/kg bw
95% CL:
1 216 - 1 789
Sex:
male
Dose descriptor:
LD50
Effect level:
1 876 mg/kg bw
95% CL:
1 359 - 2 590
Mortality:
Mortality was observed (see table 1 and 2).
Clinical signs:
1250 - 2250 mg/kg bw: clonic convulsion, piloerection, salivation, dyspnoea, tremor, high stepping gait, nose discharge, hollow flanks. The signs were observed till 7 days of the observation period. In the females of 1000 mg/kg bw dose group, slight gasping was observed.
Body weight:
There was no effects on the body weight gain in all dose groups.
Gross pathology:
Deceased animals: redness in the lungs and gastro-intestinal tract, enlarged liver
Sacrificed animals: no abnormalities were detected

Table 1: Mortality rate in males

Dose (mg/kg bw)

Mortality rate

Died within

312

0/5

-

1000

0/5

-

1250

0/5

-

1600

3/5

6 h

2000

2/5

4 h

2250

4/5

5 h

Table 2: Mortality rates in females

Dose (mg/kg bw)

Mortality rate

Died within

312

0/5

-

1000

1/5

3 h

1250

0/5

-

1600

4/5

6 h

2000

4/5

4 h

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 for male and female rats was reported to be 1876 and 1475 mg/kg bw, respectively.
Executive summary:

This study was performed according to guideline and GLP. The LD50 for male and female rats was reported to be 1876 and 1475 mg/kg bw, respectively. Significant mortality was observed from the dose level of 1600 mg/kg bw within 6 h after exposure. Clinical signs were clonic convulsion, piloerection, salivation, dyspnoea, tremor, high stepping gait, nose discharge, hollow flanks. The signs were persistent until the end of the 7 days observation period. At necropsy, redness in the lungs and gastro-intestinal tract, and enlarged liver were described.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Two groups of 3 rabbits per dose were treated simultaneously by gavage with preparations of the test substance in suitable vehicle. The concentrations of these preparations were used to achieve comparable volumes per kg body weight. Group-wise documentation of clinical signs was performed.
GLP compliance:
no
Test type:
standard acute method
Species:
rabbit
Strain:
not specified
Sex:
not specified
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 3-15%
Doses:
300, 1000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Sex:
not specified
Dose descriptor:
LD50
Effect level:
300 - 1 000 mg/kg bw
Mortality:
1000 mg/kg bw: All 3 rabbits died within 24 h after dosing.
300 mg/kg bw: No mortalities were observed
Clinical signs:
1000 mg/kg bw: spasmodic muscle convulsions, opithotonus, tonic-clonic cramps and lateral position
300 mg/kg bw: no signs were observed
Gross pathology:
no alterations were observed
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 was found to be 300-1000 mg/kg bw in rabbits.
Executive summary:

Rabbits were exposed to 300, 1000 mg/kg bw of the test substance. After treatment with 1000 mg/kg bw, all 3 rabbits died within 24 h after dosing. After treatment with 300 mg/kg bw, no mortalities were observed. Therefore, the LD50 value has been found to be 300 -1000 mg/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
BASF-Test: In principle, the methods described in the OECD Guideline 401 were used. Young adult laboratory rats were purchased from breeder. Usually the source and strain of animals were not documented. Several groups of 5-15 rats per sex and dose were treated simultaneously by gavage with preparations of the test substance in suitable vehicle. The concentrations of these preparations were used to achieve comparable volumes per kg body weight. Group-wise documentation of clinical signs was performed over the 7 day study period. Body weight was determined before the start of the study only, as it was needed for determination of dose.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Heigl rats
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Mean body weight at study initiation:
200 mg/kg bw: male 179 g (153-204 g) female 153 g (145-157 g)
640 mg/kg bw: male 188 g (154-204 g) female 169 g (144-185 g)
800 mg/kg bw: male 201 g (157-234 g) female 175 g (171-190 g)
1000 mg/kg bw: male 213 g (157-240 g) female 169 g (134-192 g)
1250 mg/kg bw: male 196 g (153-260 g) female 173 g (143-200 g)
1600 mg/kg bw: male 165 g (136-225 g) female 160 g (135-200 g)
2000 mg/kg bw: male 214 g (125-280 g) female 161 g (134-187 g)
2500 mg/kg bw: male 174 g (147-220 g) female 166 g (140-183 g)
3200 mg/kg bw: male 195 g (170-220 g) female 167 g (134-187 g)
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2, 16 %

DOSAGE PREPARATION:
- Stock solution prepared: 2% for 200 mg/kg bw dose group; 16% for 640, 800, 1000, 1250, 1600, 2000, 2500, 3200 mg/kg bw dose groups
- Dose volume applied: 10 ml/kg bw of the 2 % stock solution for 200 mg/kg bw dose group. 4, 5, 6.25, 7.8, 10, 12.5, 16.0 and 20 ml/kg bw of the 16 % stock solution for 640, 800, 1000, 1250, 1600, 2000, 2500 and 3200 mg/kg bw dose groups, respectively.
Doses:
200, 640, 800, 1000, 1250, 1600, 2000, 2500, 3200 mg/kg bw
No. of animals per sex per dose:
5 each for 200 mg/kg bw dose groups;
10 each for 640, 800, 1000, 1250, 2000, 2500, 3200 mg/kg bw dose groups;
15 each for 1600 mg/kg bw dose group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: mortality and clinical signs of toxicity were observed several times on the application day and thereafter once each working day, body weights were only recorded at the beginning of the study.
- Necropsy of survivors performed: yes
Statistics:
Method of Litchfield and Wilcoxon
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 660 mg/kg bw
95% CL:
1 420 - 1 940
Mortality:
Mortality was observed (see tables 1 and 2).
Clinical signs:
agitation, hyperexcitability, tonic-clonic convulsions, oral secretion and dyspnoea were observed after dosing. After 3 days, the animals were without symptoms.
Body weight:
no data
Gross pathology:
no abnormalities were detected

Table 1: Mortality in males

Dose (ml/kg bw)

Mortality in (males)

1 h

24 h

48 h

7 days

3200

4/10

8/10

9/10

9/10

2500

4/10

8/10

8/10

8/10

2000

0/10

0/10

0/10

0/10

1600

0/15

4/15

4/15

4/15

1250

0/10

3/10

4/10

4/10

1000

0/10

1/10

1/10

1/10

800

0/10

0/10

0/10

0/10

640

0/10

0/10

0/10

0/10

200

0/5

0/5

0/5

0/5

Table 2: Mortality in females

Dose (ml/kg bw)

Mortality in (females)

1 h

24 h

48 h

7 days

3200

4/10

9/10

10/10

10/10

2500

6/10

10/10

10/10

10/10

2000

0/10

9/10

9/10

9/10

1600

0/15

6/15

6/15

6/15

1250

0/10

1/10

5/10

5/10

1000

0/10

0/10

0/10

0/10

800

0/10

0/10

0/10

0/10

640

0/10

0/10

0/10

0/10

200

0/5

0/5

0/5

0/5

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 value was found to be 1660 mg/kg bw in rats.
Executive summary:

Male and female heigl rats were exposed to 200, 640, 800, 1000, 1250, 1600, 2000, 2500, 3200 mg/kg bw of the test substance. The duration of observation period following administration was 7 days. The LD50 value was found to be 1660 mg/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
5 male and 5 female F344 rats were administered single doses of the test substance in corn oil by gavage. All surviving animals were killed after 14 days.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): Caprolactam
- Analytical purity: the results of purity and identity analyses performed at Midwest Research Institute were consistent with the structure and literature values.
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: NCI Frederick Cancer Research Center, Frederick, Maryland
- Age at study initiation: 3 weeks
- Acclimation period: 2 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-26
- Humidity (%): 30-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12


Route of administration:
oral: gavage
Vehicle:
corn oil
Doses:
681, 1000, 1470, 2150, 3160 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
Sex:
female
Dose descriptor:
LD50
Effect level:
1 210 mg/kg bw
Sex:
male
Dose descriptor:
LD50
Effect level:
1 650 mg/kg bw
Mortality:
Mortality was observed (see table 1).

Table 1: Survival rate of males and females

Dose

(mg/kg bw)

Survival rate (number surviving/number per group)

Male

Female

681

5/5

5/5

1000

5/5

4/5

1470

3/5

1/5

2150

1/5

0/5

3160

0/5

0/5

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 values were found to be 1210 mg/kg bw for females rats and 1650 mg/kg bw for males rats.
Executive summary:

Male and female Fischer 344 rats were exposed to 681, 1000, 1470, 2150, 3160 mg/kg bw of the test substance. The duration of observation period following administration was 14 days. The LD50 values were found to be 1210 mg/kg bw for females and 1650 mg/kg bw for males.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 475 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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
no GLP
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
Groups of 10 Wistar rats/sex were exposed to a liquid aerosol of the test substance (50%, w/w) using a head-nose inhalation system.
GLP compliance:
no
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: Dr. K. Thomae GmbH, Biberach
- Age at study initiation: 8 weeks
- Mean weight at study initiation: male 250 g (224-268 g) female 178 g (161-192 g)
- Diet (e.g. ad libitum): Kliba labor diet
- Water (e.g. ad libitum): tap water


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12


Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
other:
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose/head - inhalation system INA 20, BASF AG
- Exposure chamber volume: 55 l
- Method of holding animals in test chamber: animals were kept in the tube with muzzle projecting in the inhalation chamber
- System of generating particulates/aerosols: Generatorsystem- infusion pump INFU 362, membrane dose pump Duramat. The aerosol was generated using compressed air.
- Temperature in air chamber: 19-25 °C


TEST ATMOSPHERE
- Brief description of analytical method used: Quantitative determination of aerosol concentration was performed using gas chromatography. For this the aerosol probes were dissolved in 10ml Ethanol.
- Samples taken from breathing zone: yes
- Nominal concentrations were calculated using the substance consumption and the air volume.
- probes for particle size analysis were taken from 30 min after onset of exposure

VEHICLE
- Concentration of test material in vehicle: 50% (w/v) in water




Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5.25, 8.35 and 10.12 mg/l
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weight of individual animals was measured before treatment and after 7 and 14 days of treatment, daily clinical inspection
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology (anatomical/pathological)
Statistics:
According to the probit analysis of D.J. Finney, 1-150 (Syndics of the Cambridge University Press, 1971).
Sex:
male/female
Dose descriptor:
LC50
Effect level:
8.16 mg/L air
95% CL:
7.2 - 9.23
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
ca. 9.6 mg/L air (analytical)
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
7.08 mg/L air (analytical)
95% CL:
5.87 - 8.1
Exp. duration:
4 h
Mortality:
Mortality was observed (see table 1).
Clinical signs:
other: Symptoms during exposure: closure of eyelid, irregular respiration, escape reaction Symptoms after exposure: dyspnoea, piloerection, intermittent respiration, bloody nose and eye discharge, tremor. Clinical signs were reversible after 5 days (low dose), 7
Body weight:
No effects on body weight gain were observed
Gross pathology:
Severe hyperemia in lungs and liver adiposis in some perished animals. No abnormalities in the sacrificed animals
Other findings:
- Histopathology: fatty degeneration in the liver and ischemic tubulonephrosis in the cortex of the kidney of 1 deceased animal. No lesions were observed in the sacrificed animals.

Table 1: Mortality of males and females.

Dose (mg/l)

Sex

Mortality within

4 h

1 day

14 days

5.25

M

0/10

1/10

1/10

F

0/10

1/10

1/10

8.25

M

0/10

1/10

1/10

F

0/10

7/10

7/10

10.12

M

2/10

7/10

7/10

F

1/10

10/10

10/10

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The LC50 value for male/female rats was determined to be 8.16 mg/l.
Executive summary:

This study was performed similar to the OECD guideline 403. Rats were exposed to a liquid aerosol of the test substance using a head-nose inhalation system at analytical concentrations of 5.25, 8.35 and 10.12 mg/l for 4 hours. Exposure related mortalities were observed at all dose levels and the LC50 for male/female was determined to be 8.16 mg/l.

Observed clinical signs of toxicity were indicative for irritation (eyelid closure, irregular respiration, escape reaction during exposure and dyspnoea, piloerection, bloody nose and eye discharge and tremor after exposure). Clinical signs were reversible with 7 days post exposure.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
816 000 mg/m³

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:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
occlusive dressing instead of semi-occlusive
Qualifier:
equivalent or similar to guideline
Guideline:
other: 84/449/EWG (Official Journal of EU, Nr. L251 from 19.09.1984, p 103)
Deviations:
yes
Remarks:
occlusive dressing instead of semi-occlusive
GLP compliance:
yes
Remarks:
(Bayer AG, Institute of Toxicology)
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): Epsilon-Caprolactam
- Physical state: solid
- Analytical purity: 99.9%
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen
- Age at study initiation: male 9 weeks, female 14 weeks
- Mean weight at study initiation: male 230 g, female 211 g
- Diet (e.g. ad libitum): Altromin 1324 pellets
- Water (e.g. ad libitum): tap water
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 50±10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12


Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- % coverage: 10%
- Type of wrap if used: The treated area was covered and fixed with aluminum foil


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


TEST MATERIAL
- 3ml/kg bw test substance was applied
Duration of exposure:
24 h
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: Body weight of individual animals was measured before treatment and after 7 and 14 days of treatment, daily clinical inspection
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no mortalities were observed
Clinical signs:
no clinical signs were observed
Body weight:
Delayed weight gain in some animals.
Gross pathology:
no abnormalities were observed
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 value has been found to be greater than 2000 mg/kg bw in rats.
Executive summary:

This study is a limit dose test with rats performed similar to guideline with GLP. 24 h of dermal exposure to 2000 mg/kg bw under occlusive conditions resulted in no mortalities or signs of toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Oral exposure route:

In the key study (Bayer, 1987) performed according to guideline and GLP, the LD50 for male and female rats was reported to be 1876 and 1475 mg/kg bw, respectively. Significant mortality was observed from the dose level of 1600 mg/kg bw within 6 h after exposure. Clinical signs were clonic convulsion, piloerection, salivation, dyspnoea, tremor, high stepping gait, nose discharge, hollow flanks. The signs were persistent until the end of the 7 days observation period. At necropsy, redness in the lungs and gastro-intestinal tract, and enlarged liver were described.

These findings were supported by further acute oral studies in which LD50 values of 1650 and 1210 mg/kg bw for male and female rats, respectively (NTP, 1982), and 1660 mg/kg bw (BASF AG, 1965) were reported. Both studies also supported the finding of the test substance being a convulsant poison when applied in high oral doses.

Regarding acute oral toxicity in further species, LD50 values in the range of 300-1000 mg/kg bw were reported for rabbits and cats (BASF AG, 1965) and 2070 and 2490 mg/kg bw for male and female mice, respectively (NTP, 1982).

In addition, few studies with limited documentation (Reliability 4) reported LD50 values of 1155 mg/kg bw (Bornmann, 1959) and 3375 mg/kg bw (Dupont 1950) in rats, 1200 mg/kg bw in mice (Hohensee, 1959), and 1000 mg/kg bw in rabbit and mice (Lomonova, 1986).

 

Dermal exposure route:

The key study is a limit dose test with rats performed according to guideline with GLP (Bayer, 1987). 24 h of dermal exposure to 2000 mg/kg bw under occlusive conditions resulted in no mortalities or signs of toxicity.

Further studies of limited reporting and experimental quality were identified in the database:

for rabbits LD50 values of 3375 mg/kg (DuPont, 1950) and 1520 mg/kg bw were reported (occlusive exposure for 24 h, Smyth et al., 1969).

 

Inhalation exposure route:

In the key study performed similar to the guideline 403, rats were exposed to a liquid aerosol of the test substance using a head-nose inhalation system at analytical concentrations of 5.25, 8.35 and 10.12 mg/l for 4 hours (BASF AG, 1985). Exposure related mortalities were observed at all dose levels and the LC50 for male/female was determined to be 8.16 mg/l.

Observed clinical signs of toxicity were indicative for irritation (eyelid closure, irregular respiration, escape reaction during exposure and dyspnoea, piloerection, bloody nose and eye discharge and tremor after exposure). Clinical signs were reversible with 7 days post exposure.

Experimental quality and reporting of all further acute inhalation experiments was insufficient. LC50 values of 0.45 mg/l (Lomonova, 1961) or >2.98 mg/l (DuPont, 1950) were reported for the aerosol in mice or rats, respectively. But no analysis of the exposure atmosphere was performed and various undefined exposure equipments and times were chosen.

One experiment is addressing the toxicity of a saturated vapor concentration of the test substance (0.0061 mg/l) in mice. Minimal signs of sensory irritation were reported (DuPont, 1997). 

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. The LD50 after oral expsosure was found to be 1876 mg/kg bw (male) and 1475 mg/kg bw (female), the LC50 after inhalative exposure 8.16 mg/l (male/female) and the LD50 after dermal exposure >2000 mg/kg bw (rat).

Based on the LC50 of 8.16 mg/L for male/female rats (aerosol), no classification is required. However, the test substance is officially classified as acute tox. Category 4 according to CLP regulation. This official classification is finally taken in to account.

As a result, the test substance is considered to be classified for acute oral toxicity Categorie 4 and for acute inhalative toxicity Categorie 4 under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No 2018/1480.