Bromobenzene

Endpoint summary

Description of key information

Skin irritation (rabbit): irritating

Eye irritation (rabbit): not irritating

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:

Oct - Nov 1982

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

Please refer to analogue justification provided in IUCLID section 13

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

28 Jul 2015

Deviations:

yes

Remarks:

no initial test was performed

GLP compliance:

no

Species:

rabbit

Strain:

other: HC:NZW

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hacking & Churchill Ltd., Huntingdon, UK
- Weight at study initiation: about 3000 g
- Housing: individual housing under standardized coditions
- Diet: Ssniff K (Versuchstierdiäten GmbH, Soest, Germany), ad libitum
- Water: Tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 40 - 60
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated sites of the same animal served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL
- Concentration: 100%

Duration of treatment / exposure:

4 h

Observation period:

14 days
Reading time points: 1, 24, 48 and 72 h and 6 days

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: 6 x 6 cm on the dorsal area of the trunk
- Type of wrap if used: The treated skin was covered with an elastic and air permeable bandage

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test material was removed with water
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
1, 24, 48 and 72 h and 6 days

SCORING SYSTEM:
- Method of calculation: Draize scoring system

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 6 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 6 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 6 days

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 6 days

Irritant / corrosive response data:

All animals showed moderate erythema and slight edema on the application sites that were fully reversible within 6 days.

Table 1: Results of skin irritation

Observation time	Rabbit no.
	1		2		3
	Erythema	Edema	Erythema	Edema	Erythema	Edema
1 h	3	0	3	0	2	0
24 h	3	1	3	1	2	1
48 h	3	1	3	1	2	1
72 h	3	1	3	1	2	1
Mean value 24 + 48 + 72 h	3,00	1,00	3,00	1,00	2,00	1,00
6 d	0	0	0	0	0	0

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

CLP: Skin Irrit 2, H315

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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:

Nov 1982

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

Please refer to the analogue approach justification document provided in section 13

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

02 Oct 2012

Deviations:

yes

Remarks:

no topical anesthetics and systemic analgesics were used; no initial test was performed

GLP compliance:

no

Species:

rabbit

Strain:

other: HC:NZW

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hacking & Churchill Ltd., Huntingdon, UK
- Weight at study initiation: about 3000 g
- Housing: individual housing under standardized coditions
- Diet: Ssniff K (Versuchstierdiäten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 40 - 60
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the same animal served as control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL
- Concentration: 100%

Duration of treatment / exposure:

24 h

Observation period (in vivo):

21 days
Reading time points: 1, 24, 48 and 72 h and 7 days

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: the treated eye was rinsed with NaCl solution
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal: #1, #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritant / corrosive response data:

All animals showed mild to moderate (graded with scores of 1 - 2) conjunctival redness and swelling after test substance instillation. In one animal slight opacity of the cornea was observed at the 1 and 24 h reading time points. All effects were fully reversible latest within 7 days. No further substance-related effects were observed.

Table 1: Individual scores

Rabbit #	Time [h]	conjunctivae		iris	cornea
		redness	swelling
1	1	1	1	0	0
	24	1	1	0	0
	48	1	0	0	0
	72	1	0	0	0
	average	1.0	0.3	0.0	0.0
2	1	2	1	0	1
	24	2	1	0	1
	48	1	1	0	0
	72	0	0	0	0
	average	1.0	0.7	0.0	0.3
3	1	1	1	0	0
	24	1	1	0	0
	48	1	0	0	0
	72	0	0	0	0
	average	0.7	0.3	0.0	0.0
	Time [h]	conjunctivae		iris	cornea
		redness	swelling
average score	1	1.33	1.00	0.00	0.33
	24	1.33	1.00	0.00	0.33
	48	1.00	0.33	0.00	0.00
	72	0.33	0.00	0.00	0.00
	24+48+72	0.89	0.44	0.00	0.11

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation(EC) No. 1272/2008.

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Irritation

 

There are no data available on skin and eye irritating properties of bromobenzene (CAS 108-86-1). Thus, read-across from an appropriate substance is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. in order to fulfil the standard information requirements defined in Regulation (EC) No 1907/2006, Annex VII, 8.1 and 8.2. Structural similarities and comparable toxicokinetic properties of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Skin irritation

CAS 108 -90 -7

The skin irritancy potential of chlorobenzene was determined in a skin irritation study performed similar to OECD 404 (reference 7.3.1-1). The test substance was topically applied to the shaved skin of three rabbits (NZW) for 4 h. Local reactions were scored at 1, 24, 48 and 72 h and 6 days after substance application. All animals showed moderate erythema and slight edema on the application sites (mean erythema scores of 3, 3 and 2 for the 3 animals over 24, 48 and 72 h; mean edema scores of 1 for all 3 animals over 24, 48 and 72 h) that were fully reversible within 6 days. Based on the results of the conducted study, chlorobenzene exhibits irritating properties towards the skin.

In conclusion, based on the analogue approach, bromobenzene is considered as skin irritant and meets the classification criteria for skin irritation, category 2 according to Regulation (EC) 1272/2008.

 

Eye irritation

CAS 108 -90 -7

To evaluate the irritation potential towards the eyes, 0.1 mL chlorobenzene (undiluted) was instilled into the eyes of 3 white rabbits (NZW) (reference 7.3.2-1). 24 hrs after test substance instillation, the eyes were rinsed with physiological saline solution. The eyes were observed 1, 24, 48, 72 and 168 h after treatment. All animals showed mild to moderate conjunctival redness (graded with scores of 1 - 2) and swelling (graded with score 0 - 1) resulting in mean scores of 1, 1, and 0.7 for conjunctivae and 0.3, 0.7 and 0.3 for chemosisfor all 3 animals over 24, 48 and 72 h, respectively. In one animal slight opacity of the cornea was observed after 1 and 24 h, resulting in a mean score of 0.3 over 24, 48 and 72 h. All effects were fully reversible latest within 7 days. Based on the results of the conducted study, chlorobenzene is considered as not irritating to the eyes.

In conclusion, based on the analogue approach, bromobenzene is not considered to exhibit eye irritating properties.

Justification for classification or non-classification

Based on the analogue approach, the available data on skin irritation meets the criteria for classification as Skin Irrit. Cat. 2 (H315) according to Regulation (EC) 1272/2008.

Based on the analogue approach, the data on eye irritation does not meet the classification criteria for eye irritation according to Regulation (EC) 1272/2008.