Registration Dossier

Administrative data

Description of key information

- Skin irritation: not irritating (OECD 404; LAB Research Ltd., 2009);
- Eye irritation: severe irreversible lesions (similar to OECD 405, BASF, 1967).

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
Study period:
2009-08-25 to 2009-08-28
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
(Hungarian GLP Regulations: 9/2001. (III. 30.) EÙM-FVM joint decree of the Minister of Health and the Minister of Agriculture and Regional Development which corresponds to the OECD GLP, ENV/MC/CHEM (98) 17
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: S&K-LAP Kft., Hungary
- Age at study initiation: 10 weeks
- Weight at study initiation: at the beginning of the study: 4532-4689 g; at the end of the study 4589-4749 g
- Housing: Rabbits were individually housed in AAALC approved metal wire rabbit cages (65x65 cm with height of 45 cm, on 2 levels with a shelf to allow rabbits to climb up to stretch out). Cages are of an open wire structure and cages are placed together to allow some social interaction with rabbit(s) in adjoining cages
- Diet (e.g. ad libitum): ad libitum (PURINA Base - Lap gr. diet for rabbits produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi ut, Hungary)
- Water (e.g. ad libitum): ad libitum (municipal tap water)
- Acclimation period: 62 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.2-22.7
- Humidity (%): 34-70
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 24 June 2009 ( date of receipt) To: 2009-08-28
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated skin of each animal served as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:
4 hours
Observation period:
at 1, 24, 48 and 72 hours after the patch removal
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: not reported
- coverage: 6 cm²
- Type of wrap if used: The trunk was wrapped in clear plastic with medical tubing used to hold the patch in place.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: After the treatment period, the test item was removed with body temperature water.

SCORING SYSTEM:
Scoring and Assessment of Local Reactions:
The dermal irritation scores were evaluated according to the scoring system by Draize (1959). The animals were observed for 72 hours, the duration of the study was sufficient to evaluate fully the reversibility or irreversibility of the effects observed.

Erythema and eschar formation:
No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar
formation (injuries in depth) 4
Maximum possible erythema score: 4

Oedema formation:
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of it will be well defined
by definite raising) 2
Moderate oedema (raised appr. 1 mm) 3
Severe oedema (raised more than 1 mm and extending
beyond area of exp.) 4
Maximum possible oedema score: 4
Irritation parameter:
erythema score
Remarks:
(mean)
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Remarks:
(mean)
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Remarks:
(mean)
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Remarks:
(mean)
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Remarks:
(mean)
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Remarks:
(mean)
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
At observation one hour after patch removal, well defined erythema (score 2) was observed in one animal, very slight erythema (score 1) was found in one animal and very slight oedema (score 1) was found in two animals.
At 24 hours after patch removal, very slight erythema (score 1) was found in one animal and very slight oedema (score 1) was found in two animals.
At 48 and 72 hours after patch removal, there were no observed signs on the skin of the treated animals.
As no clinical signs were observed up to 72 hours after patch removal, the study was terminated after the 72 hour observation.
The animals' individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema were 0.00, 0.00 and 0.33 respectively.
The animals' individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for oedema were 0.33, 0.33 and 0.00 respectively.
Other effects:
There was no mortality observed during the study.
There was no effect of treatment on body weight.
There were no treatment-related clinical signs noted.

Table 1. Scoring for erythema formation

Animal No./ Sex

Body weight (g)

at the beginning of the study

at the end of the study

1 h

24 h

48 h

72 h

13/ M

4689

4749

0

0

0

0

10/ M

4633

4715

1

0

0

0

6/ M

4532

4589

2

1

0

0

TOTAL

-

-

3

1

0

0

Table 2. Scoring for oedema formation

Animal No./ Sex

Body weight (g)

at the beginning of the study

at the end of the study

1 h

24 h

48 h

72 h

13/ M

4689

4749

1

1

0

0

10/ M

4633

4715

1

1

0

0

6/ M

4532

4589

0

0

0

0

TOTAL

-

-

2

2

0

0

Table 3. Mean values of skin irritation scores (24, 48, 72 hours reading)

Animal Number

Sex

Erythema

Oedema

13

male

0.00

0.33

10

male

0.00

0.33

6

male

0.33

0.00

Interpretation of results:
GHS criteria not met
Conclusions:
According to Directive 2001/59/EC, Vantex T does not require classification as a skin irritant.
According to the UN Globally Harmonised System of Classification and Labelling of Chemicals, Vantex T does not require classification as a skin irritant.
Executive summary:

An acute skin irritation study of the test item Vantex T was performed in New Zealand White rabbits. Parameters monitored during this study included mortality, body weight measurements and clinical observations. The irritation effects of the test item were evaluated according to the Draize method (OECD No.: 404, 2002).

The test item was administered undiluted, at a single dose of 0.5 ml. Gauze was placed onto the hairless skin of the rabbit, test item was applied to the gauze, additional gauze was placed over the test item and an adhesive clear plastic patch applied. The trunk was wrapped in clear plastic with medical tubing used to hold the patch in place. The untreated skin of each animal served as control.

After 4 hours, the remaining test item was removed with water of body temperature.

To assess skin irritation, animals were examined at 1, 24, 48 and 72 hours after the patch removal. Additional general examinations were performed daily.

There was no mortality or systemic clinical changes related to Vantex T administration.

There was no effect of treatment on body weight.

At observation one hour after patch removal, well defined erythema (score 2) was observed in one animal, very slight erythema (score 1) was found in one animal and very slight oedema (score 1) was found in two animals.

At 24 hours after patch removal, very slight erythema (score 1) was found in one animal and very slight oedema (score 1) was found in two animals.

At 48 and 72 hours after patch removal, there were no observed signs on the skin of the treated animals.

As no clinical signs were observed up to 72 hours after patch removal, the study was terminated after the 72 hour observation.

The animals' individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema were 0.00, 0.00 and 0.33 respectively.

The animals' individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for oedema were 0.33, 0.33 and 0.00 respectively.

According to Directive 2001/59/EC, Vantex T does not require classification as a skin irritant.

According to the UN Globally Harmonised System of Classification and Labelling of Chemicals, Vantex T does not require classification as a skin irritant.

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
Study period:
1967
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an acceptable BASF-test which in principle is similar to OECD 405 (1981), with some deviations (the eyes were not washed out after 24 h); GLP was not compulsory at the time the study was conducted.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
1981
Deviations:
yes
Remarks:
eyes were not washed out after 24 h of treatment
Principles of method if other than guideline:
BASF Test:
Before OECD guideline 405 was established, eye irritation was tested using an BASF internal method. White Vienna rabbits were used. Usually approximately 50 µL of the unchanged test material were applied into the conjunctival sac of one eye of each of 2 animals. The non- or saline- treated eye served as control.The animals were observed several times on the treatment day and up to 8 days afterwards, and findings were recorded on working days. The eyes were not washed out after 24 h as specified in OECD Guideline 405.
GLP compliance:
no
Remarks:
GLP was not compulsory at the time the study was conducted
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
Weight at study initiation: 3.19 and 2.83 kg
Vehicle:
unchanged (no vehicle)
Controls:
other: the second eye was treated with NaCl
Amount / concentration applied:
0.05 mL
Duration of treatment / exposure:
The test substance were applied unchanged to the rabbit eyes, and the eyes were not washed out.
The eyes were examined after

Observation period (in vivo):
8 days
reading time points: after 10 minutes, 1 h, 3 h, 24 h, 48 h and 72 h, and at day 6, 7 and 8.
Number of animals or in vitro replicates:
one male and one female animal
Details on study design:
Following application, the animals were examined for corneal changes, iris effects and conjunctival reaction at the reading time points mentioned above. The eye findings, which had been originally scored according to a BASF scoring system were re-evaluated according to the Draize Scoring System.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: same finding at all reading time points given above
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: same finding at all reading time points given above
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: constricted pupil, bleeding, detachment of the upper skin layer, bloody discharge, grey-brown signs of corrosion; same findings at all reading time points given above
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: slight swelling, same finding at all reading time points given above
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: same finding at all reading time points given above
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: same finding at all reading time points given above
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: constricted pupil, bleeding, detachment of the upper skin layer, bloody discharge, grey-brown signs of corrosion; same findings at all reading time points given above
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: swelling, same finding at all reading time points given above
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of the 2 animals
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
mean
Remarks:
of the 2 animals
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of the 2 animals
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of the 2 animals
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
not reversible
Irritant / corrosive response data:
Animal 1:
At day 6, findings were as already described with in addition, scarring at the upper eyelid.
At day 7, findings were as already described with in addition, scarring at the upper eyelid, conjunctiva becoming grey-white, bleeding, slight to milky opacity of the cornea, and vascular ingrowth.
At day 8, findings were as reported above, with in addition onset of staphyloma; thus there was no evidence for reversibility of the findings.
Control eyes treated with physiological saline remained free from effects.

Animal 2:
At day 6, findings were as already described with in addition, scarring at the upper eyelid, slight to milky opacity of the cornea, vascular ingrowth and onset of staphyloma.
At day 7, findings were similar as for day 6.
At day 8, findings were as reported above, with clear staphyloma; thus there was no evidence for reversibility of the findings.
Control eyes treated with physiological saline remained free from effects.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
CLP: Cat 1
DSD: R 34
Executive summary:

Butyldiethanolamine was tested for eye irritation in the rabbit according to an internal BASF method, which in principle was similar to the OECD TG 405 (1981). Approximately 50 µL of the unchanged test material were applied into the conjunctival sac of one eye of each of 2 rabbits. The saline-treated eye served as control.The animals were observed several times on the treatment day and up to 8 days afterwards, and findings were recorded on working days. The eyes were not washed out after 24 h as specified in OECD Guideline 405. The findings were evaluated according to the Draize Scoring System.

The instillation of the test material into the eye of rabbit resulted in severe irreversible lesions.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

A study was conducted to assess skin irritation potential of Butyldiethanolamine in Vienna White rabbits (OECD 404; BASF, 1967, Report No. XVII/49). Two animals (1 male / 1 female) were treated for 1, 5, 15 minutes and for 20 hours using occlusive conditions. The test item was applied unchanged on the dorsal skin of each rabbit by means of a test patch. An application site of 2.5 x 2.5 cm was covered with the liquid test substance and maintained in place over the exposure period. The untreated skin area of the test animals served for control. In addition, the test item also was applied onto the ear for 20 hours. The results from the ear, however, would not be taken into account for evaluation as they do not represent testing of the dorsal/lateral flank of the back. After the application time, the skin was washed with water which sometimes contained a mild detergent (1, 5 and 15 minutes). Following the 20 hour application, the skin was not washed after removal of the dressing. The animals were observed for 8 days. Skin reaction was recorded after 1, 24, 48, 72, 96 h and after 7 and 8 days after patch removal. The evaluation of the skin findings was performed according to the Draize Scoring System. Only the scorings referring to the 20 hour treatment of the skin were considered for assessment.

At the end of the observation period of 8 days, the 20 h-treated skin of both animals displayed severe necrosis (in one case: leathery aspect) and scaling. Taking into account the 20 h duration of treatment, the findings give evidence for the test item to be corrosive to the skin of rabbit. This is further supported by the results of the short term applications (1, 5, 15 minutes). Regarding the first animal, after application for 1 or 5 minutes, respectively, questionable redness (grade 1) was reported; this however was no more seen after 24 hours. After the 15 minutes treatment, questionable redness (grade 1) was seen until reading time point 48 h, and became more defined after 72 h (grade 2); scaling was still seen at the end of the observation period of 8 days. Regarding the second animal, treatment for 1 and 5 minutes resulted in questionable redness (grade 1) lasting until reading time point 72 h. Treatment for 15 minutes resulted in questionable to well defined redness (grade 1 - 2), accompanied by crusting, present until day 7 of observation.

Regarding the ear which was treated for 20 hours, redness of grade 1 and 3 was reported for the first and second animal, respectively. No further skin reaction was seen until the end of the observation period of 8 days.

The skin reactions gave evidence for the test item to be corrosive to the skin of rabbit under the test conditions used.

Butyldiethanolamine was tested in a second acute skin irritation study in New Zealand White rabbits (LAB Research Ltd., 2009, Report No. 09/189 -006N). Parameters monitored during this study included mortality, body weight measurements and clinical observations. The irritation effects of the test item were evaluated according to the Draize method (OECD No.: 404, 2002). The test item was administered undiluted, at a single dose of 0.5 mL under semi-occlusive conditions. The untreated skin of each animal served as control. After 4-hour exposure period, the remaining test item was removed with water of body temperature. The animals were examined at 1, 24, 48 and 72 hours after the patch removal for skin irritation responses. Additional general examinations were performed daily. There was no mortality or systemic clinical changes related to the test material administration. There was no effect of treatment on body weight.

At observation one hour after patch removal, well defined erythema (score 2) was observed in one animal, very slight erythema (score 1) was found in one animal and very slight oedema (score 1) was found in two animals.

At 24 hours after patch removal, very slight erythema (score 1) was found in one animal and very slight oedema (score 1) was found in two animals.

At 48 and 72 hours after patch removal, there were no observed signs on the skin of the treated animals.

As no clinical signs were observed up to 72 hours after patch removal, the study was terminated after the 72 hour observation.

The animals' individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema were 0.00, 0.00 and 0.33 respectively.

The animals' individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for oedema were 0.33, 0.33 and 0.00 respectively.

In conclusion, Butyldiethanolamine does not meet the criteria for classification as irritant or corrosive according to EU classification and labelling Regulations since all scores were under the cut-off value of 2.3. No symbol and risk phrase are required. The corrosive result from the BASF-study is more than worst case. A 20-h exposure time from this study cannot be evaluated comparing to 4 -hour exposure in the more recent OECD guideline conform study (LAB Research Ltd., 2009). Moreover, the exposure was under occlusive conditions in the BASF study while semi-occlusive conditions were in the LAB Research Ltd. study. Therefore, the BASF study results can be disregarded.

Eye irritation

Butyldiethanolamine was tested for eye irritation in the rabbit according to an internal BASF method (BASF, 1967; Report No. XVII/49), which in principle was similar to the OECD TG 405 (1981). Approximately 50 µL of the unchanged test material were applied into the conjunctival sac of one eye of each of 2 rabbits. The saline-treated eye served as control.The animals were observed several times on the treatment day and up to 8 days afterwards, and findings were recorded on working days. The eyes were not washed out after 24 h as specified in OECD Guideline 405. The findings were evaluated according to the Draize Scoring System.

The instillation of the test material into the eye of rabbit resulted in severe irreversible lesions.


Justification for selection of skin irritation / corrosion endpoint:
GLP guideline study properly conducted: exposure time 4 hours under semi-occlusive conditions.

Justification for selection of eye irritation endpoint:
One study available

Effects on eye irritation: corrosive

Justification for classification or non-classification

Skin irritation

According to the classification criteria outlined in the section 3.2.2.2. (Guidance on the Application of CLP criteria, 2013), if the mean value of2.3 -4.0 was reached for erythema/eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal, the classification as Skin Irritant would be assigned. The highest value for erythema/eschar and oedema was 1.0 in each of three animals at 24 -h, 48 -h or 72 -h reading points (LAB Research Ltd., 2009). The mean values of 0.00, 0.00 and 0.33 for erythema and 0.33, 0.33 and 0.00 for oedema were measured in animal 1, 2 and 3, respectively. Therefore, Butyldiethanolamine does not meet criteria under Regulation (EC) No 1272/2008 for classification and labelling as a skin irritant.

Eye irritation

Butyldiethanolamine caused irreversible damage to the eyes of rabbits. Therefore, the substance should be classified and labelled as seriously damaging to eyes (Category 1, H318) according to Regulation (EC) No 1272/2008.