Registration Dossier

Diss Factsheets

Administrative data

Description of key information

skin: rabbit, OECD 404, GLP: not irritating (BASF 1998)
eye: rabbit, OECD 305, GLP: irritating (reversible), (BASF 1998)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Animals: New Zealand White (SPF)
Age: Young adult animals
Acclimatization period: At least one week.
Room temperature/relative humidity: The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 20 - 24 degrees celsius for temperature and of 30-70 % relative humidity. There were no deviations from these ranges wgich influenced the results of the study.
Day/night rhythm: 12 h/12 h (6.00 A.M. - 6.00 P.M./6.00 P.M. - 6.00 A.M.)
Type of cage: Stainless steel wire mesh cages with grating, floor area 3000 cm2.
No. of animals per cage: Single housing.
Bedding: No bedding in the cages; sawdust in the waste trays.
Drinking water: About 250 ml tap water per animal per day.
Diet: Kliba-Labordiet, Klingentalmuehle AG, Kaiseraugst, Switzerland. About 130 g per animal per day.
Analysis of drinking water: The drinking water is regularly assayed for chemical contaminants by the municipal authorities of Frankenthal and the technical services of BASF Aktiengesellschaft as well as for the presence of germs by a contract laboratory.
Analysis of feed: The feed used in the study was assayed for chemical and microbiological contaminants.
Type of coverage:
semiocclusive
Preparation of test site:
other: clipping of the fur
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of the same animal
Amount / concentration applied:
0.5 ml of test substance
Duration of treatment / exposure:
4 h
Observation period:
15 days
Number of animals:
3
Details on study design:
At least 24 hours before the test, the fur was removed by clipping the dorsal part of the trunk of the animals. Only animals with healthy intact skin have been used.
Weight determination: Shortly before application of the test substance.
Route of application: The test substance was applied in a single dose to the intact untreated skin. The test patch was secured in position with a semiocclusive dressing. The test substance was removed at the end of the exposure period with Lutrol(R) and Lutrol(R)/Water (1:1).
Application volume: The test patch (2.5x2.5 cm) was moistened with a dose of 0.5 ml of the at about 80 centrigrade heated test substance. Before application it was cooled down to body temperature.
Application side: Upper third of the back or flanks.
Readings: 1 h, 24 h, 48 h. 72 h, 8 d, and 15 d after removal of the patch.
Mortality: A check for any dead or moribund animal was made twice each workday and once on saturdays, sundays, and on public holidays.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-48-72 h
Score:
1.2
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24-48-72 h
Score:
1.3
Reversibility:
not fully reversible within: 15 d
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24-48-72 h
Score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24-48-72 h
Score:
1.3
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-48-72 h
Score:
0
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Animals: New Zealand White (SPF)
Age: Young adult animals
Acclimatization period: At least one week.
Room temperature/relative humidity: The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 20 - 24 degrees celsius for temperature and of 30-70 % relative humidity. There were no deviations from these ranges wgich influenced the results of the study.
Day/night rhythm: 12 h/12 h (6.00 A.M. - 6.00 P.M./6.00 P.M. - 6.00 A.M.)
Type of cage: Stainless steel wire mesh cages with grating, floor area 3000 cm2.
No. of animals per cage: Single housing.
Bedding: No bedding in the cages; sawdust in the waste trays.
Drinking water: About 250 ml tap water per animal per day.
Diet: Kliba-Labordiet, Klingentalmuehle AG, Kaiseraugst, Switzerland. About 130 g per animal per day.
Analysis of drinking water: The drinking water is regularly assayed for chemical contaminants by the municipal authorities of Frankenthal and the technical services of BASF Aktiengesellschaft as well as for the presence of germs by a contract laboratory.
Analysis of feed: The feed used in the study was assayed for chemical and microbiological contaminants.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
15 d
Number of animals or in vitro replicates:
3
Details on study design:
Both eyes of the animals were examined before application of the test material for signs of pre-existing irritation, reaction or abnormality which would prevent it from being used in the study.
Acclimatization period: At least 1 week.
Weight determination: Shortly before application of the test substance.
Route of application: Single application to the conjunctival sac of the right eyelid. The substance was washed out with tap water about 24 hours after application (before 24 hour reading).
Application volume: 0.1 ml of the at about 80 degrees centigrade heated test substance. Before application it was cooled down to body temperature.
Observation period: 15 d.
Readings: 1 h, 24 h, 48 h, 72 h, 8 d, and 15 d after application.
Mortality: A check for any dead or moribund animal was made twice each workday and once on saturdays, sundays, and on public holidays.
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24-48-72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24-48-72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24-48-72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24-48-72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 15 d
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24-48-72 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 15 d
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24-48-72 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 15 d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24-48-72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 8 d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24-48-72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 8 d
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24-48-72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 15 d
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-48-72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-48-72 h
Score:
0.2
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24-48-72 h
Score:
2.6
Max. score:
3
Reversibility:
fully reversible within: 15 d
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-48-72 h
Score:
1.2
Reversibility:
fully reversible within: 15 d
Irritant / corrosive response data:
No effects on the cornea were observed.
In one animal an effect on the iris after 24 h and 48 h after application was observed, which was fully reversible within 72 h.
Conjunctivae redness was markedly increased from 1 h to 8 d after application in all 3 animals. These effects were fully reversible within 15 d.
Chemosis was observed in all 3 animals after 1 h and 24 h.Between 48 h and 72 only 2 animals showed chemosis. After 15 d no chemosis was observed in any animal. Discharge was observed in all animals between 1 h and 72 h. After 8 day discharge was only seen in 1 animal which also suffered from suppuration. After 15 d discharge was fully reversible in all animals and also suppuration of one animal was reversible.
Details see table 1.

Table 1: Irritation/Corrosion scores after treatment of animals with test substance.

 Readings  Animal Cornea-opacity Cornea-area  Iris Conjunctiva-Red  Conjunctiva-swelling   Conjunctiva-discharge
 1 h  01  0  0  2  1  3
   02  0  0  2  2  3
   03  0  0  2  2  2
 24 h  01  0  0  3  2  2
   02  0  0  3  1  1
   03  0  1  3  2  3
 48 h  01  0  0  2  1  1
   02  0  0  3  0  1
   03 0  1  3  2  3
 72 h  01 0  0  2  1  1
   02  0  0  2  0  1
   03  0  0  2  2  1
 8 d  01  0  0  1  0  1
   02  0  0  1  0  0
   03  0  1  1  0
 15 d  01  0  0  0  0  0
   02  0  0  0  0  0
   03  0  0  0  0  0
               
 Mean 01   0.0  0.0  2.3  1.3  
  02  0.0  0.0  2.7  0.3  
  03  0.0    0.7  2.7  2.0  
 Mean    0.0    0.2  2.6  1.2  
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There are relevant and reliable data available investigating the skin and eye irritation of 1-Butanaminium, N,N-dibutyl-N-methyl-, methyl sulfate.

Skin:

OECD Guideline Study:

The potential of 1-butanaminium, n,n-dibutyl-n-methyl-, methyl sulfate to cause acute dermal irritation or corrosion was assessed by a single topical application of 0.5 ml of the test substance to the intact skin of 3 white new zealand rabbits for 4 hours under semiocclusive dressing according to OECD guideline 404 under GLP. The average score (24 to 72 hours) for irritation was calculated to be 1.2 (1.3; 1; 1.3) for erythema and 0.0 for edema. The skin findings were reversible in 2 animals after 72 hours or 8 days, while erythema was still present in 1 animal at study termination (15 days after removal of the patches). Hence under the test conditions chosen and considering the described findings 1-butanaminium, n,n-dibutyl-n-methyl-, methyl sulfate does not give indication of an irritant property to the skin (BASF 1998).

Eye:

OECD Guideline Study:

The potential of 1-butanaminium, n,n-dibutyl-n-methyl-, methyl sulfate to cause damage to the conjunctiva, iris or cornea was assessed in 3 white new zealand rabbits, subjected to a single ocular application of 0.1 ml of the test substance on day 0 according to OECD guideline 405 under GLP.The average score (24 to 72 hours) for irritation was calculated to be 0.0 for corneal opacity, 0.2 (0; 0; 0.67) for iris, 2.6 (2.33; 2.67; 2.67) for conjunctivae redness and 1.2 (1.33; 0.33; 2) for chemosis. The findings were reversible in all animals within 15 days after application. Symptom observed and described in the respective observation in detail together with the average score for irritation indicates an irritant property of the test substance to the eye. Hence, under the test conditions chosen and considering the described findings 1-butanaminium, n,n-dibutyl-n-methyl-, methyl sulfate gives indication of an irritant property to the eye (BASF, 1998).

As there is only one reliable and relevant study available for each endpoint and no further information indicate anymore critical results, these studies were integrated as key study.

Assessment for skin and eye irriation:

Based on the available studies on skin and eye irritation the substance is not skin irritating but eye irritating

(according to actual classification guidelines).


Effects on eye irritation: irritating

Justification for classification or non-classification

Based on the above information and according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, a classification of the substance as skin irritant is not justified but for eye irritant a classification is necessary.

Skin:

-GHS: no classification

-DSD: no classification

Eye

-GHS: CAT 2A, H319

-DSD: Xi, R36