Registration Dossier

Administrative data

Description of key information

- skin irritation:             not irritating  for the rabbit skin; Shell Development Company (1980A) / key (rabbit skin irritation) 
- eye irritation: irritating for the rabbit eye; Shell Development Company (1980B) / key (rabbit skin irritation)
- respiratory irritation: no test available

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: - relatively short summary of results - secondary source - relative high amount (8%) of unknown impurities in the test item
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
: scoring at 24, 72 and 7 d post treatment
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Ranch Rabbit Crawley, Sussex, UK
- no further information available
Type of coverage:
occlusive
Preparation of test site:
other: intact shaved skin and abraded skin
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): 100 %

Duration of treatment / exposure:
24 h
Observation period:
7
Number of animals:
4 males + four females
Details on study design:
TEST SITE
- Area of exposure: backs, 2 x 2 cm² abraded using a hypodermic needle (deep enough to disturb stratum corneum, but without bleeding)
- % coverage: 2 x 2 cm² abraded skin and 2 x 2 cm² intact skin
- Type of wrap if used: lint patches, covered by occlusive polyethylene film, fixed in place with 3'' Protoplast adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no


SCORING SYSTEM: Draize score system:
Erythema
No erythema = 0
Pale pink = 1
Redness = 2
Severe redness = 3
Beet redness = 4
Oedema
No oedema = 0
Soft skin = 1
Oedema = 2
More definite oedema = 3
Severe oedema = 4
Irritation parameter:
erythema score
Basis:
animal: 1, 2
Time point:
other: 24/72 h; no observation at 48 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
animal: 5
Time point:
other: 24/72 h; no observation at 48 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
animal: 6
Time point:
other: 24/72 h; no observation at 48 h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24/72 h; no observation at 48 h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24/72 h; no observation at 48 h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: 24/72 h; no observation at 48 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: intct skin
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: 24/72 h; no observation at 48 h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: intact skin
Irritant / corrosive response data:
Moderate to severe erythema and edema were seen at all time points in all exposed animals (see Table for details)
Other effects:
none reported

- Table 1: Individual scores for erythema (E) and Oedema (O)

Rabbit number and sex

Response

Abraded skin

Non abraded skin

24 hours

72 hours

7 days

24 hours

72 hours

7 days

E

O

E

O

E

O

E

O

E

O

E

O

1 M

2

3

2-3

2

3

3

2

3

2

1-2

2

2

2 M

4

3

4

2

3

2

2

2-3

2

2

2-3

2

5 F

1-2

2

2

1-2

3

3

4

3

4

2-3

4

2

6 F

2

1-2

1-2

1

3

2

2

2

0-1

0-1

2

1

Mean

2.4

2.5

2.5

1.6

3.0

2.5

2.5

2.6

2.1

1.6

2.6

1.8

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
New Zealand White rabbits (4 males, 4 females) were treated with technical grade 1,2,3-trichloropropane for 24 h under occlusive conditions to assess the skin irritation potential following essentially OECD TG 404. Moderate to severe erythema and edema were seen at all time points in all exposed animals. Based on this results this technical grade 1,2,3-trichloropropane is deemed a skin irritant.
Executive summary:

In the present study Clark 1977 New Zealand White rabbits were treated once with 0.5 mL undiluted 1,2,3 -trichloropropane dermaly under occlusive conditions on shaved skin for 24 h and analysed for skin reactions, body weight development and clinical signs following generally the OECD TG 404. The purity of the test item was only 92 %.

Maximal erythema scores of 4 and edema scores of 3 were reached, not reversible until 7 d post end of treatment.

Based on this result 1,2,3 -trichloropropane would be classified as skin irritant Category 2 (H315: Causes skin irritation) according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.

New Zealand White rabbits, young adult animals,4 males and 4 female were used for the test. Undiluted test material (0.5 ml) was applied to the shaved backs (intact and abraded) of test animals. The area was wrapped with gauze and occluded for 24 hours with plastic sheeting. All animals were observed at 24, and 72 hours, and at days 7 post-dosing.

Moderate to severe erythema and edema were seen at all time points in all exposed animals. Based on this results this technical grade 1,2,3-trichloropropane is deemed a skin irritant. The relevance of this result for pure 1,2,3 -trichloropropane is questionable as the composition of the impurities (total of 8 %) and their influence on the test result is unclear. Therefore this study is deemed unreliable.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: - followed recognized toxicology testing procedures - GLP compliant - study results copied without further assessment from the SIDS dossier
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
other: FIFRA Pesticide Assessment Guidelines, Subdivision F, 81-5 (1978 and 1982) and TSCA, Health Effects Test Guidelines, Primary Dermal Irritation. Appears to follow OECD 404 for Dermal Irritation (although not specified)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Age at study initiation: young adult,
- Weight at study initiation: males: not reported in SIDS dossier
- Fasting period before study: not reported in SIDS dossier
- Housing: not reported in SIDS dossier
- Diet (e.g. ad libitum): not reported in SIDS dossier
- Water (e.g. ad libitum): not reported in SIDS dossier
- Acclimation period: not reported in SIDS dossier

ENVIRONMENTAL CONDITIONS
- not reported in SIDS dossier
Type of coverage:
other: 4h exposure: semi-occlusive; 24 h exposure: occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): undiluted


VEHICLE
- no vehicle used
Duration of treatment / exposure:
4h semi-occlusive and 24 h occlusive
Observation period:
All animals were observed at 0.5, 24, 24.5, 48 and 72 hours, and at days 7 and 10 post-dosing.
Number of animals:
5 males and 1 female
Details on study design:
TEST SITE
- Area of exposure: back
- % coverage: not reported in the SIDS report
- Type of wrap if used: area wrapped with gauze and semi-occluded for 4 hours; while the 24-hour exposure was completely occluded with plastic sheeting.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): backs were gently wiped with dry gauze when the bandages were removed
- Time after start of exposure: 4 h for semi-occlusive conditions, 24 h for occlusive conditions


SCORING SYSTEM:
probably Draize score system, not detailed in SIDS report
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 4 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 4 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 10 d
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritant / corrosive response data:
Irritation was mild and transient at both sites (i.e. those semi-occluded for 4 hours and those occluded for 24 hours). Four-hour erythema scores reached a high of 2, clear by day 7 to 10; 4-hour edema scores were generally 1, clear by 72 hours. Twenty-four-hour erythema scores were 2, clear by day 7 to 10; 24-hour edema scores were 1, clear by day 7
Other effects:
One of 6 rabbits was found dead on day 5. No explanation was reported, although a post mortem examination was conducted.
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal irritating effects of 1,2,3-trichloropropane was tested in rabbits using a recognized scientific procedure and followed recognized GLP procedures. Maximal erythema scores of 2 and edema scores of 1 were reached, completely reversible between 3 to 10 days.
Executive summary:

In the present study ( Monsanto Company, 1985A) male and female New Zealand White rabbits were treated once with 0.5 mL undiluted 1,2,3 -trichloropropane dermaly under occlusive conditions on shaved skin for 24 h and analysed for skin reactions, body weight development and clinical signs following generally the OECD TG 404 in compliance with GLP.

Maximal erythema scores of 2 and edema scores of 1 were reached, completely reversible between 3 to 10 days.

Based on this result 1,2,3 -trichloropropane is not classified regarding skin irritation according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.

New Zealand White rabbits, young adult animals,5 males and 1 female were used for the test. Undiluted test material (0.5 ml) was applied to the shaved backs of test animals. The area was wrapped with gauze and semi-occluded for 4 hours; while the 24-hour exposure was completely occluded with plastic sheeting. Their backs were gently wiped with dry gauze when the bandages were removed. All animals were observed at 0.5, 24, 24.5, 48 and 72 hours, and at days 7 and 10 post-dosing.

One of 6 rabbits was found dead on day 5. No explanation was reported, although a post mortem examination was conducted. Irritation was mild and transient at both sites (i.e. those semi-occluded for 4 hours and those occluded for 24 hours). Four-hour erythema scores reached a high of 2, clear by day 7 to 10; 4-hour edema scores were generally 1, clear by 72 hours. Twenty-four-hour erythema scores were 2, clear by day 7 to 10; 24-hour edema scores were 1, clear by day 7.

The primary irritation index was 2.5. Individual scores for edema and erythema were recorded from 4.5 hours to 10 days post-dosing.

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: - followed recognized toxicology testing procedures - GLP compliant - study results copied without further assessment from the SIDS dossier
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
other: Consistent with NAS Publication 1138 dtd 1977; Draize scoring method
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: not reported
- Age at study initiation: not reported in SIDS dossier
- Weight at study initiation: 2 - 2.8 Kg
- Fasting period before study: not reported in SIDS dossier
- Housing: not reported in SIDS dossier
- Diet (e.g. ad libitum): not reported in SIDS dossier
- Water (e.g. ad libitum): not reported in SIDS dossier
- Acclimation period: not reported in SIDS dossier


ENVIRONMENTAL CONDITIONS
- not reported in SIDS dossier
Type of coverage:
occlusive
Preparation of test site:
other: two groups: abraded and shaved respectively
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): undiluted


VEHICLE
- no vehicle used
Duration of treatment / exposure:
24 h
Observation period:
7 d after end of exposure
Number of animals:
3 per sex and form of exposure (shaved/abraded)
Details on study design:
TEST SITE
- Area of exposure: backs were shaved and one half of the test animals were further prepared by abrading their backs (deep enough to penetrate the stratum corneum but not to the derma).
- % coverage: not reported in SIDS dossier
- Type of wrap if used: The area was wrapped with gauze and occluded with clear polyethylene film.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): backs were gently wiped with a moist towel
- Time after start of exposure: 24 h

SCORING SYSTEM:
Draize score system

The primary irritation index is calculated by the addition of erythema scores and oedema scores of all animals at observation time points, divided by the number of animals X the number of time points.


Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: not reported in detail in SIDS report, probably 24h and 72 h after end of treatment
Score:
1.63
Max. score:
4
Reversibility:
other: edema were reversible within 72 h, reversibility of erythema is not clear from the summary in the SIDS report
Irritant / corrosive response data:
Erythema was present through 72 hours in abraded skin sties, and 24 hours in unabraded sites. Edema, which was observed initially and at 24 hours, was clear by 72 hours in both groups. The severity of the response was greater in the abraded test sites. Individual scores ranged from 1-2.5 in intact skin, and from 1-3 in abraded skin sites. Overall PII was 1.63 and was mildly irritating.
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal irritating effects of 1,2,3-trichloropropane was tested in rabbits using a recognized scientific procedure and followed recognized GLP procedures. An overall primary irritation index for abraded and shaved skin of 1.63 was observed.
Executive summary:

In the present study (Shell Development Company, 1980c) male and female New Zealand White rabbits were treated once with 0.5 mL undiluted 1,2,3 -trichloropropane dermaly under occlusive conditions on abraded and shaved skin for 24 h and analysed for skin reactions, body weight development and clinical signs following generally the OECD TG 404 in compliance with GLP.

An overall primary irritation index (PII) for abraded and shaved skin of 1.63 was observed.

Based on this result 1,2,3 -trichloropropane is not classified regarding skin irritation according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.

Undiluted test material (0.5 ml) was applied to the shaved backs of test animals; six rabbits were further prepared by abrading their backs (deep enough to penetrate the stratum corneum but not to the derma). The area was wrapped with gauze and occluded with clear polyethylene film for 24 hours. After 24 hours the bandages were removed and the test sites were observed for erythema and edema. Their backs were then gently wiped with a moist towel. All animals were again observed at 72 hours, and at day 7.

Erythema was present through 72 hours in abraded skin sites, and 24 hours in unabraded sites. Edema, which was observed initially and at 24 hours, was clear by 72 hours in both groups. The severity of the response was greater in the abraded test sites. Individual scores ranged from 1-2.5 in intact skin, and from 1-3 in abraded skin sites. Overall PII was 1.63.

The authors state the substance as mildly irritating but according to CLP no classification is needed based on this PII.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: - relatively short summary of results - secondary source - relative high amount (8%) of unknown impurities in the test item
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
other: Federal Register, 28 (110), 6.6.1963. para. 191.12
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Ranch Rabbit Crawley, Sussex, UK
- no further information available
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): not reported in detail, but as the method of Draize is cited, it is assumed that 0.1 mL were instilled
- Concentration (if solution): 100%

Duration of treatment / exposure:
treated once
Observation period (in vivo):
1 to 2 hours after instillation and again at 1, 2, 3 and 7 days, thence every 4 days until eye irritancy was no longer observed
Number of animals or in vitro replicates:
4
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize score system

TOOL USED TO ASSESS SCORE: not reported
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: average of results from readings at 24, 48 and 72 h post dosing
Score:
0.1
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: based on opacity only, not on area
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: average of results from readings at 24, 48 and 72 h post dosing
Score:
0.2
Max. score:
3
Reversibility:
fully reversible within: 2 d
Remarks on result:
other: redness only
Irritation parameter:
iris score
Basis:
mean
Time point:
other: average of results from readings at 24, 48 and 72 h post dosing
Score:
0
Max. score:
2
Reversibility:
fully reversible
Irritant / corrosive response data:
Some mild irritating effects were caused by the instillation of technical grade 1,2,3-trichloropropane. A slight opacity remained beyond day 7 in one animal (for details see Table 1).
Other effects:
Immediately on instillation into the rabbit eyes there was obvious pain.

Table 1: Mean response to instillation of 0.1 mL 1,2,3-trichloropropane, technical grade

 

Mean response

 

1-2 hours

1 day

2 days

3 days

7 days

Conjunctiva

 

 

 

 

 

  Redness

1

0.6

0

0

0

  Chemosis

1

0.3

0

0

0

  Discharge

0.5

0

0

0

0

Cornea

 

 

 

 

 

  Opacity

0

0.1

0

0.1

0.1

  Area

0

0.5

0

0.5

0.5

Iris

0

0

0

0

0

Interpretation of results:
GHS criteria not met
Conclusions:
0.1 mL of 1,2,3-trichloropropane (technical grade 92 %) was instilled into the eyes of New Zealand White rabbits in order to test the eye irritation potency of this test item following essentially OECD TG 405. Slight conjunctiva redness and chemosis and slight cornea opacity was seen 24 h post treatment. A slight opacity remained beyond day 7 in one animal. Based on this results this technical grade 1,2,3-trichloropropane is deemed a slight eye irritant, nevertheless not fulfilling the criteria for CLP classification.
Executive summary:

In the present study Clark 1977 New Zealand White rabbits were treated once with 0.1 mL undiluted 1,2,3 -trichloropropane (instillation to one eye) and analysed for eye irritation following generally the OECD TG 405. The purity of the test item was only 92 %. Slight conjunctiva redness and chemosis and slight cornea opacity was seen 24 h post treatment. A slight opacity remained beyond day 7 in one animal. Based on this result 1,2,3 -trichloropropane is not classified as eye irritant according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.

4 New Zealand White rabbits, young adult animals, were used for the test. Undiluted test material (0.1 ml) was applied to the eye sac of one eye of test animals. All animals were observed at 1 -2 h, 24, 48 and 72 hours, and at days 7 post-dosing and thence every 4 d until the irritation completely subsided.

Slight conjunctiva redness and chemosis and slight cornea opacity was seen 24 h post treatment. A slight opacity remained beyound day 7 in one animal.

The relevance of this result for pure 1,2,3 -trichloropropane is questionable as the compostition of the impurities (total of 8 %) and their influence on the test result is unclear. Therefore this study is deemed unreliable.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: - followed recognized toxicology testing procedures - GLP compliant - study results copied without further assessment from the SIDS dossier
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
other: FIFRA Pesticide Assessment Guidelines, Subdivision F, 81-4 (1982) and TSCA, Health Effects Test Guidelines, Acute Exposure, Primary Eye Irritation. Appears to follow OECD 405 for Primary Eye Irritation (although not specified).
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS

- Age at study initiation: not reported in SIDS dossier
- Weight at study initiation: males: not reported in SIDS dossier
- Fasting period before study: not reported in SIDS dossier
- Housing: not reported in SIDS dossier
- Diet (e.g. ad libitum): not reported in SIDS dossier
- Water (e.g. ad libitum): not reported in SIDS dossier
- Acclimation period: not reported in SIDS dossier

ENVIRONMENTAL CONDITIONS
- not reported in SIDS dossier
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): undiluted


VEHICLE
- no vehicle used
Duration of treatment / exposure:
continuous, no washing-out of the substance
Observation period (in vivo):
Eyes were evaluated for irritation at 1, 24, 48 and 72 hours and at 7 days
Number of animals or in vitro replicates:
3 males and 3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no washing out


SCORING SYSTEM:
- not reported in the SIDS report, probably Draize score system

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
other: 3 of 6 animals
Time point:
other: not reported in detail in the SIDS report
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
other: 3 of 6 animals
Time point:
other: not reported in detail in the SIDS report
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 3 d
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: not reported in detail in the SIDS report
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
other: all animals
Time point:
other: not reported in detail in the SIDS report
Score:
>= 1 - <= 3
Max. score:
4
Reversibility:
not specified
Irritant / corrosive response data:
Corneal opacity/ulceration and iritis were present in 3/6 rabbits through 72 hours, clear by day 7. Maximum score for opacity was 2 in one rabbit, while 1/6 had a score of 1 and 1/6 was + (positive). Opacity clear by day 7. Minimal ulceration (score of 1 or +) was reported in 3/6 rabbits. Iritis scores in 3/6 rabbits reached a maximum score of 1; clear in 72 hours. Involvement of the conjunctiva reported for 6/6 rabbits; clear in 7 days or less. Redness, chemosis and discharge were observed in 6/6 rabbits, with scores ranging from 1-3. Test material was considered moderately irritating.
Other effects:
no other effects reported
Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Conclusions:
The eye irritating effects of 1,2,3-trichloropropane was tested in rabbits using a recognized scientific procedure and followed recognized GLP procedures. Maximal chemosis scores of 1-3, cornea scores of 2, iris scores of 1 and conjuctivae scores completely reversible between 3 and 7 days.
Executive summary:

In the present study ( Monsanto Company, 1985B) 0.1 mL of undiluted 1,2,3 -trichloropropane was instilled once to the eye of male and female New Zealand White rabbits without washing-out and analysed for eye reactions, body weight development and clinical signs following generally the OECD TG 404 in compliance with GLP.

Maximal chemosis scores of 1-3, cornea scores of 2, iris scores of 1 and conjuctivae scores of 1 are reported, that are completely reversible between 3 and 7 days.

As no detailed individual data is available from the SIDS dossier in a conservative approach 1,2,3 -trichloropropane is classified as Category 2 ( Causes serious eye irritation) regarding eye irritation according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.

3 male and 3 female New Zealand White rabbits were tested. Test material (0.1 ml) was placed into the everted lower eyelids of 3 male and 3 female New Zealand White rabbits. Treated eyes of all animals were unwashed. Eyes were evaluated for irritation at 1, 24, 48 and 72 hours and at 7 days. Corneas were reexamined at the same time periods with sodium fluorescein. Animals were housed individually.

Corneal opacity/ulceration and iritis were present in 3/6 rabbits through 72 hours, clear by day 7. Maximum score for opacity was 2 in one rabbit, while 1/6 had a score of 1 and 1/6 was + (positive). Opacity clear by day 7. Minimal ulceration (score of 1 or +) was reported in 3/6 rabbits. Iritis scores in 3/6 rabbits reached a maximum score of 1; clear in 72 hours. Involvement of the conjunctiva reported for 6/6 rabbits; clear in 7 days or less. Redness, chemosis and discharge were observed in 6/6 rabbits, with scores ranging from 1-3. Test material was considered moderately irritating.

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: - followed recognized toxicology testing procedures - GLP compliant - study results copied without further assessment from the SIDS dossier
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
other: consistent with NAS Publication 1138 dtd 1977); Draize scoring method
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: not reported
- Age at study initiation: not reported in SIDS dossier
- Weight at study initiation: 2 - 2.9 Kg
- Fasting period before study: not reported in SIDS dossier
- Housing: 1 per cage
- Diet (e.g. ad libitum): not reported in SIDS dossier
- Water (e.g. ad libitum): not reported in SIDS dossier
- Acclimation period: not reported in SIDS dossier


ENVIRONMENTAL CONDITIONS
- not reported in SIDS dossier

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): undiluted


VEHICLE
- no vehicle used
Duration of treatment / exposure:
unwashed eye: continuous
washed eyes: washed out after 30 s
Observation period (in vivo):
Treated eyes of all animals were evaluated for irritation at 1, 6, 24, 72 hours and at 7 and 14 days
Number of animals or in vitro replicates:
3 male and 3 female New Zealand White rabbits; another 3 male rabbits received the same treatment but the eyes were washed 30 seconds after instillation with tap water
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): 3 of 9 animals, with tap water
- Time after start of exposure: 30 s after start of exposure


SCORING SYSTEM:
Draize score system/eye irritation scoring by Kay and Calandra
Treated eyes of all animals were evaluated for irritation at 1, 6, 24, 72 hours and at 7 and 14 days.

TOOL USED TO ASSESS SCORE: Corneas were reexamined at the same time periods with 0.2% sodium fluorescein. Animals were housed individually
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: not reported in detail in the SIDS report
Score:
20
Max. score:
110
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: animals without wash-out; maximal overall irritation scores for individual animals were not reported in the SIDS report
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: not reported in detail in the SIDS report
Score:
16.3
Max. score:
110
Reversibility:
not fully reversible within: 7 d
Remarks on result:
other: animals without wash-out; maximal overall irritation scores for individual animals were not reported in the SIDS report
Irritant / corrosive response data:
Superficial corneal ulcerations were detected in 4/6 unwashed eyes by 1 hour and in 5/6 by 6 hours; it was also observed in 2/3 washed eyes at 24 hours. The corneal ulceration reversed within 72 hours. Iritis was observed in 5/6 unwashed (clear in 72 hours) and 1/3 washed (clear in 24 hours). Some conjunctival irritation remained in both groups for 7 days (1/6 and 1/3, respectively). A maximum score of 20/110 was reported for unwashed eyes, and 16.3/110 for washed eyes. Test material was considered moderately irritating.
Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Conclusions:
The irritating effects of 1,2,3-trichloropropane to the rabbit eye was tested using a recognized scientific procedure and followed recognized GLP procedures. A maximum overall irritation score of 20/110 was reported for unwashed eyes, and 16.3/110 for washed eyes.
The test material was considered moderately irritating by the authors of the study.
Executive summary:

In the present study (Shell Development Company, 1980d) male and female New Zealand White rabbits got 0.1 mL undiluted 1,2,3 -trichloropropane instilled into one eye and were analysed for eye irritation effects, body weight development and clinical signs for 14 d following generally the OECD TG 405 in compliance with GLP.

A maximum overall irritation score of 20/110 was reported for unwashed eyes, and 16.3/110 for washed eyes. The test material was considered moderately irritating by the authors of the study.

As no detailed individual data is available from the SIDS dossier in a conservative approach 1,2,3 -trichloropropane is classified as Category 2 ( Causes serious eye irritationr) regarding eye irritation according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.

Nine rabbits, 3 males and 3 females in the unwashed group; 3 males in the washed group were tested. Test material (0.1 ml) was placed into the everted lower eye lid of 3 male and 3 female New Zealand White rabbits; another 3 male rabbits received the same treatment but the eyes were washed 30 seconds after instillation with tap water. Treated eyes of all animals were evaluated for irritation at 1, 6, 24, 72 hours and at 7 and 14 days. Corneas were reexamined at the same time periods with 0.2% sodium fluorescein. Animals were housed individually.

Superficial corneal ulcerations were detected in 4/6 unwashed eyes by 1 hour and in 5/6 by 6 hours; it was also observed in 2/3 washed eyes at 24 hours. The corneal ulceration reversed within 72 hours. Iritis was observed in 5/6 unwashed (clear in 72 hours) and 1/3 washed (clear in 24 hours). Some conjunctival irritation remained in both groups for 7 days (1/6 and 1/3, respectively). A maximum score of 20/110 was reported for unwashed eyes, and 16.3/110 for washed eyes. Test material was considered moderately irritating by the authors of the study..

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

- skin irritation: The classification of the key parameter (not irritating to the rabbit skin) is based on results of the study Shell Development Company (1980A) / key (rabbit skin irritation) considered to be fully reliable and compliant to OECD TG 404 by the SIDS INITIAL ASSESSMENT REPORT For SIAM 18 - 1,2,3-Trichloropropane as at 2004. The result is backed up by a similar rated and study (Monsanto Company (1985A) / (rabbit, skin irritation)).
Both studies agree that there is some slight intermittent irritancy caused by 1,2,3-trichloropropane that is also reversible within 72 h in the former and within 10 at the latest in the latter study. In the former study overall PII was 1.63, while individual scores ranged from 1-2.5 in intact skin, and from 1-3 in abraded skin sites.In the latter study our-hour erythema scores reached a high of 2, clear by day 7 to 10; 4-hour edema scores were generally 1, clear by 72 hours. Twenty-four-hour erythema scores were 2, clear by day 7 to 10; 24-hour edema scores were 1, clear by day 7.
The differing results from Clark 1977, reporting skin irritancy after application of 1,2,3-trichloropropane to the rabbit skin are very likely due to the relative high amount of unknown impurities (8 %). Due to the lack of information on the nature of these impurities the study is deemed unreliable.
Therefore 1,2,3 -trichloropropane is deemed not to be a skin irritant which is in-line with the current classification and labelling.

- eye irritation: The classification of the key parameter (irritation to the rabbit eye) is based on the results of the study Shell Development Company (1980B) / key (rabbit eye irritation) considered to be fully reliable and compliant to OECD TG 405 by the SIDS INITIAL ASSESSMENT REPORT For SIAM 18 - 1,2,3-Trichloropropane as at 2004. The results are backed up by a similar rated and study (Monsanto Company (1985B) / (rabbit, eye irritation)). Both studies agree that 1,2,3-trichloropropane is slightly irritating to the rabbit eye, the former reportinga maximum overall irritation score of 20/110 for unwashed eyes, and 16.3/110 for washed eyes. The latter study states maximal chemosis scores of 1-3, cornea scores of 2, iris scores of 1 and conjuctivae scores of 1, which are all completely reversible between 3 and 7 days. The presented values are relatively low and might have supported a non-classification for eye irritation. But as individual data is not available and following a conservative approach, 1,2,3-trichloropropane is deemed irritating to the eye.
The differing results from Clark 1977, reporting slight eye irritancy after application of 1,2,3-trichloropropane to the rabbit eye are very likely due to the relative high amount of unknown impurities (8 %). Due to the lack of information on the nature of these impurities the study is deemed unreliable.

- respiratory irritation: no study available.


Effects on eye irritation: irritating

Justification for classification or non-classification

- skin irritation: Based on the above stated results 1,2,3-trichloropropane is deemed not to be irritating to the skin according to CLP as implementation of UN GHS in the EU (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL).

- eye irritation: Based on the above stated results 1,2,3-trichloropropane is deemed irritating to the eye Category 2 (Warning, H319: Causes serious eye irritation) according to CLP as implementation of UN GHS in the EU (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL).

- respiratory irritation: No study available