Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.43 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEL
Value:
330 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
497.28 mg/m³
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Default value (ECHA) (subacute to chronic study)
AF for interspecies differences (allometric scaling):
1
Justification:
rat versus human: According to table R.8-4 in chapter R.8 of the ECHA guidance document (version 2.1, November 2012) the AF of 4 is already included in the route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Default value (ECHA)
AF for intraspecies differences:
5
Justification:
Default value (ECHA)for worker
AF for the quality of the whole database:
1
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are performed according to guideline and GLP.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.54 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
330 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Default value (ECHA) (subacute to chronic study)
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (ECHA) for rat versus human
AF for other interspecies differences:
2.5
Justification:
Default value (ECHA)
AF for intraspecies differences:
5
Justification:
Default value (ECHA) for worker
AF for the quality of the whole database:
1
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are performed according to guideline and GLP.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

m-phenylene di(acetate)

(CAS No. 108-58-7)

DNELs (worker/general population)

I. Introduction:

Classification

Harmonized classification – Annex VI of Regulation (EC)  (No 1272/2008 (CLP Regulation):

Not classified

Self-classification: Eye Irrit. 2 (H319: Causes serious eye irritation), Skin Sens. 1B (H317: May cause an allergic skin reaction)

Known occupational exposure limit(s):

SCOEL: no data

TRGS 900: no data

MAK: no data

Remarks/Limitations

No remarks/limitations

DNELs (worker)

II: Conclusion - worker (systemic and local effects):

 Route of exposure

 Local effect

  Systemic effect

 Dermal (long term)

 Moderate hazard (Sensitisation)

 

DNEL = 1.54 mg/kg bw/day

Dermal (short term)

 Moderate hazard (Sensitisation)

 

No hazard identified

 Inhalation (long term)

 

No hazard identified

 

DNEL = 5.43 mg/m³

 Inhalation (short term)

 

No hazard identified

  

No hazard identified

Hazard for eyes

Low hazard band

III. DNEL systemic (worker)

Basis for delineation of the DNELs systemic:

In a OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test) three groups of ten male and ten female rats received m-phenylene di(acetate), initially at doses of 100, 330 or 1000 mg/kg/day, by oral gavage administration. From Day 5, Group 4 received m-phenylene di(acetate) at a dose level of 500 mg/kg/day due to four animals being sacrificed for welfare reasons on Day 4 of treatment. Males were treated daily for two weeks before pairing, up to necropsy after a minimum of five consecutive weeks. Females were treated daily for two weeks before pairing, throughout pairing, gestation and until Day 13 of lactation. Females were allowed to litter, rear their offspring and were killed on Day 14 of lactation.

In summary, under the conditions described the no-observed-adverse effect level (NOAEL) for oral administration of m-phenylene di(acetate) by oral gavage to male and female rats was at the dose of 330 mg/kg bw/day in males and in females. Overall, four animals (two males and two females) given 1000 mg/kg/day were killed for welfare reasons on Day 4 of treatment because of the occurrence of continuous convulsions. The cause of death of these animals was undermined, but was considered likely to be related to treatment due to the occurrence in the high dose group.

The hematological examination of blood and the biochemical examination of plasma did not reveal any effect of treatment and there was no effect upon circulating levels of thyroxine (T4) in adult males. The incidence and distribution of all macroscopic and histopathological findings were considered to be unrelated to treatment.

 Study

  NOAEL, Effects

Reference

 Title:

Resorcinol Diacetate:  Combined

Repeated Dose Toxicity Study and Reproductive/

Developmental Toxicity Screening Study in the Han

Wistar Rat by Oral Gavage Administration

Administration period:

Males: ca. 36 days

Females: ca. 54 days

Doses:

rat: ca. 0 (control), 100, 330, or 1000 mg/kg bw/day via

oral gavage (daily).       

NOAEL = 330mg/kg bw/day

Based on the following effects:

Four animals (two males and two females)

given 1000 mg/kg/day were killed for welfare

reasons on Day 4 of treatment because of the

occurrence of continuous convulsions.

The cause of death of these animals was

undermined, but was considered likely

to be related to treatment due to the occurrence

in the high dose group.

 

Froud A (2017)

Resorcinol Diacetate:  Combined Repeated Dose

Toxicity Study and Reproductive/Developmental

Toxicity Screening Study in the Han Wistar Rat

by Oral Gavage Administration

Envigo CRS Limited

Eye

Suffolk

IP23 7PX

UK

Report no.: NN75QD

 

Long-term toxicity – systemic effects (worker)

Long-term inhalation route – systemic effects (worker) using extrapolation factors:

NOAEL(oral) = 330 mg/kg bw/day (7 days a week) =  462 mg/kg bw/day (5 days a week)

Correction of the starting point according ECHA Guidance Chapter R.8:

Corrected inhalatory NOAEC = Oral NOAEL (462 mg/kg) x 1/0.38 m³/kg x 6.7 m³/10m³ x 0.5

=> NOAEC worker = 497.28 mg/m³

 Factors to be applied

Justification

 AF for dose response relationship

 

 AF for differences in duration of exposure

Default value (ECHA) (subacute to chronic study)

 AF for interspecies differences

 1

 rat versus human: According to table R.8-4 in chapter R.8 of the ECHA guidance document (version 2.1, November 2012) the AF of 4 is already included in the route to route extrapolation.

 AF for intraspecies differences

 Default value (ECHA) for worker

 AF for other interspecies differences

2.5 

  Default value (ECHA)

 

AF for quality of the whole database  

 1

 There is information available to cover all relevant toxicological endpoints. The available studies are performed according to guideline and GLP.

 

AF for remaining differences

 1

 

 

Overall factor

75 

 

 Worker DNEL long-term

for inhalation route - systemic

  

5.43 mg/m³

 

Short-term toxicity (inhalation) – systemic effects (worker)

In the key study for oral toxicity a LD50 = 4010 mg/kg bw was found. The key study for acute dermal toxicity revealed a discriminating dose of 2000 mg/kg bw.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is therefore not justified.

Therefore:

Worker DNEL short-term for inhalation exposure: no hazard identified

Long-term oral and dermal route systemic effects (worker)

NOAEL(oral) = NOAEL(dermal) = 462 mg/kg bw/day

On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) is used for oral-to-dermal extrapolation.

Factors to be applied

Justification

 AF for dose response relationship

 

 AF for differences in duration of exposure

Default value (ECHA) (subacute to chronic study)

 AF for interspecies differences

4

  Default value (ECHA) for rat versus human

 AF for intraspecies differences

 Default value (ECHA) for worker

 AF for other interspecies differences

2.5 

  Default value (ECHA)

 

AF for quality of the whole database  

 1

 There is information available to cover all relevant toxicological endpoints. The available studies are performed according to guideline and GLP.

 

AF for remaining differences

 1

 

 

Overall factor

300

 

Worker DNEL long term

for oral and dermal route - systemic

 1.54 mg/kg bw/day

Short-term toxicity (oral and dermal) – systemic effects (worker)

In the key study for oral toxicity a LD50 = 4010 mg/kg bw was found. The key study for acute dermal toxicity revealed a discriminating dose of 2000 mg/kg bw.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is therefore not justified.

Therefore:

Worker DNEL short-term for oral and dermal exposure:       no hazard identified

Reproductive Toxicity – systemic effects (worker)

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / three groups of ten male and ten female rats received m-phenylene di(acetate), initially at doses of 100, 330 or 1000 mg/kg/day, by oral gavage administration. From Day 5, Group 4 received m-phenylene di(acetate) at a dose level of 500 mg/kg/day due to four animals being sacrificed for welfare reasons on Day 4 of treatment. Males were treated daily for two weeks before pairing, up to necropsy after a minimum of five consecutive weeks. Females were treated daily for two weeks before pairing, throughout pairing, gestation and until Day 13 of lactation. Females were allowed to litter, rear their offspring and were killed on Day 14 of lactation.

The clinical condition, litter size, sex ratio, survival indices and body weight gain of offspring

were unaffected by parental treatment.

There was no effect of parental treatment upon circulating levels of thyroxine (T4) in

offspring on Day 13 of age.

The ano-gential distances of offspring were unaffected by paternal treatment and no nipples

were seen on any male offspring on Day 13 of age.

No macroscopic findings considered to be related to paternal treatment were recorded.

The no-observed adverse-effect level (NOAEL) of m-phenylene di(acetate) for systemic toxicity

was considered to be 330 mg/kg/day and the no-observed adverse-effect level (NOAEL) of

Resorcinol diacetate for reproductive/developmental toxicity was considered to be 1000/500 mg/kg/day.

In conclusion, no separate DNEL for toxicity to reproduction is required for phenylene di(acetate), as the NOAEL for toxicity to reproduction is higher than for repeated-dose toxicity.

VII. DNEL local (worker)

Basis for delineation of the DNELs local (long and short term toxicity):

Irritation/corrosion

Skin irritation:

500 mg Cohedur RK (= m-phenylene di(acetate)) were semiocclusively applied once to the intact skin (ear) of two young adult New Zealand white rabbits (3.0–4.0 kg) for an exposure period of 24 hours. Evaluation of skin irritation was made until day 7 according to Draize. Erythema and edema score was 0 at 24/48/72 hours.

In an additional in vitro skin irritation test using a human skin model, Resorcinol diacetate was non-irritant.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.

Eye irritation:

A dose of 50 mg Chohedur RK (= m-phenylene di(acetate)) was administered into one eye of two young adult New Zealand white rabbits (3–4 kg). The eyes were examined and the grade of ocular reaction was recorded until day 7 post administration according to Draize. The cornea score was 2.66, the iris score was 0.83 and the conjunctivae and chemosis score were 2.33 and 1.33, respectively. All effects were reversible within 7 days. According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Eye Irrit. 2 ( H319: Causes serious eye irritation) is justified.

Sensitization

The results of the LLNA show that the test substance elicits a SI ≥ 3. An estimated EC3 value of 21.0% was calculated.

According to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments), Resorcinol diacetate should be classified as skin

sensitizer (Category 1B) and labeled as H317: May cause an allergic skin reaction.

Conclusion on local DNEL:

For local effects:

Low hazard band for Eye Irrit. 2 ( H319: Causes serious eye irritation).

Medium hazard band for Skin sensitizer (Category 1B) (H317: May cause an allergic skin reaction).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.55 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
NOAEL
Value:
330 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
143.47 mg/m³
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Default value (ECHA) (subacute to chronic study)
AF for interspecies differences (allometric scaling):
1
Justification:
rat versus human: According to table R.8-4 in chapter R.8 of the ECHA guidance document (version 2.1, November 2012) the AF of 4 is already included in the route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Default value (ECHA)
AF for intraspecies differences:
10
Justification:
Default value (ECHA) for general population
AF for the quality of the whole database:
1
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are performed according to guideline and GLP.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.95 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
330 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Default value (ECHA) (subacute to chronic study)
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (ECHA) for rat versus human
AF for other interspecies differences:
2.5
Justification:
Default value (ECHA)
AF for intraspecies differences:
10
Justification:
Default value (ECHA) for general population
AF for the quality of the whole database:
1
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are performed according to guideline and GLP.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.95 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
330 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Default value (ECHA) (subacute to chronic study)
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (ECHA) for rat versus human
AF for other interspecies differences:
2.5
Justification:
Default value (ECHA)
AF for intraspecies differences:
10
Justification:
Default value (ECHA) for general population
AF for the quality of the whole database:
1
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are performed according to guideline and GLP.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

DNELs (general population)

V: Conclusion - general population (systemic and local effects):

 Route of exposure

  Local effect

 Systemic effect

 Oral (long term)

 No hazard identified  

 DNEL = 0.95 mg/kg bw/day

 Oral (short term)

 No hazard identified

 No hazard identified

 Dermal (long term)

 Moderate hazard (Sensitisation)

  DNEL = 0.95 mg/kg bw/day

 Dermal (short term)

 Moderate hazard (Sensitisation)

 No hazard identified

Inhalation (long term)

No hazard identified

 DNEL = 0.55 mg/m³

Inhalation (short term)

No hazard identified

No hazard identified

 Hazard for eyes

  Low hazard band

VI. DNEL systemic (general population)

Basis for delineation of the DNELs systemic:

In a OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test) three groups of ten male and ten female rats received m-phenylene di(acetate), initially at doses of 100, 330 or 1000 mg/kg/day, by oral gavage administration. From Day 5, Group 4 received m-phenylene di(acetate) at a dose level of 500 mg/kg/day due to four animals being sacrificed for welfare reasons on Day 4 of treatment. Males were treated daily for two weeks before pairing, up to necropsy after a minimum of five consecutive weeks. Females were treated daily for two weeks before pairing, throughout pairing, gestation and until Day 13 of lactation. Females were allowed to litter, rear their offspring and were killed on Day 14 of lactation.

In summary, under the conditions described the no-observed-adverse effect level (NOAEL) for oral administration of m-phenylene di(acetate) by oral gavage to male and female rats was at the dose of 330 mg/kg bw/day in males and in females. Overall, four animals (two males and two females) given 1000 mg/kg/day were killed for welfare reasons on Day 4 of treatment because of the occurrence of continuous convulsions. The cause of death of these animals was undermined, but was considered likely to be related to treatment due to the occurrence in the high dose group.

The hematological examination of blood and the biochemical examination of plasma did not reveal any effect of treatment and there was no effect upon circulating levels of thyroxine (T4) in adult males. The incidence and distribution of all macroscopic and histopathological findings were considered to be unrelated to treatment.

Long-term toxicity – systemic effects (general population)

Long-term inhalation route – systemic effects (general population) using extrapolation factors:

NOAEL(oral) = 330 mg/kg bw/day (7 days a week)

Correction of the starting point according ECHA Guidance Chapter R.8:

Corrected inhalatory NOAEC = Oral NOAEL (330 mg/kg) x 1/1.15 m³/kg x 0.5

=> NOAEC general population = 143.47 mg/m³

Factors to be applied

Justification

 AF for dose response relationship

 

 AF for differences in duration of exposure

Default value (ECHA) (subacute to chronic study)

 AF for interspecies differences

 1

 rat versus human: According to table R.8-4 in chapter R.8 of the ECHA guidance document (version 2.1, November 2012) the AF of 4 is already included in the route to route extrapolation.

 AF for intraspecies differences

10

 Default value (ECHA) for general population

 AF for other interspecies differences

2.5 

  Default value (ECHA)

 

AF for quality of the whole database  

 1

 There is information available to cover all relevant toxicological endpoints. The available studies are performed according to guideline and GLP.

 

AF for remaining differences

 1

 

 

Overall factor

150 

 

 General population DNEL long-term for inhalation route - systemic

 0.95 mg/m³

Short-term toxicity (inhalation) – systemic effects (general population)

In the key study for oral toxicity a LD50 = 4010 mg/kg bw was found. The key study for acute dermal toxicity revealed a discriminating dose of 2000 mg/kg bw.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is therefore not justified.

Therefore:

General population DNEL short-term for inhalation exposure:       no hazard identified

Long-term oral and dermal route systemic effects (general population)

NOAEL(oral) = NOAEL(dermal) = 330 mg/kg bw/day

Factors to be applied

Justification

 AF for dose response relationship

 

 AF for differences in duration of exposure

Default value (ECHA) (subacute to chronic study)

 AF for interspecies differences

4

  Default value (ECHA) for rat versus human

 AF for intraspecies differences

10 

 Default value (ECHA) for general population

 AF for other interspecies differences

2.5 

  Default value (ECHA)

 

AF for quality of the whole database  

 1

 There is information available to cover all relevant toxicological endpoints. The available studies are performed according to guideline and GLP.

 

AF for remaining differences

 1

 

 

Overall factor

600

 

General population DNEL long term

for oral and dermal route - systemic

 0.55 mg/kg bw/day

Short-term toxicity (oral and dermal) – systemic effects (general population)

In the key study for oral toxicity a LD50 = 4010 mg/kg bw was found. The key study for acute dermal toxicity revealed a discriminating dose of 2000 mg/kg bw.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is therefore not justified.

Therefore:

General population DNEL short-term for oral and dermal exposure:       no hazard identified

Reproductive Toxicity – systemic effects (general population)

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / three groups of ten male and ten female rats received m-phenylene di(acetate), initially at doses of 100, 330 or 1000 mg/kg/day, by oral gavage administration. From Day 5, Group 4 received m-phenylene di(acetate) at a dose level of 500 mg/kg/day due to four animals being sacrificed for welfare reasons on Day 4 of treatment. Males were treated daily for two weeks before pairing, up to necropsy after a minimum of five consecutive weeks. Females were treated daily for two weeks before pairing, throughout pairing, gestation and until Day 13 of lactation. Females were allowed to litter, rear their offspring and were killed on Day 14 of lactation.

The clinical condition, litter size, sex ratio, survival indices and body weight gain of offspring

were unaffected by parental treatment.

There was no effect of parental treatment upon circulating levels of thyroxine (T4) in

offspring on Day 13 of age.

The ano-gential distances of offspring were unaffected by paternal treatment and no nipples

were seen on any male offspring on Day 13 of age.

No macroscopic findings considered to be related to paternal treatment were recorded.

The no-observed adverse-effect level (NOAEL) of m-phenylene di(acetate) for systemic toxicity

was considered to be 330 mg/kg/day and the no-observed adverse-effect level (NOAEL) of

Resorcinol diacetate for reproductive/developmental toxicity was considered to be 1000/500 mg/kg/day.

In conclusion, no separate DNEL for toxicity to reproduction is required for phenylene di(acetate), as the NOAEL for toxicity to reproduction is higher than for repeated-dose toxicity.

In conclusion, no separate DNEL for toxicity to reproduction is required for phenylene di(acetate), as the NOAEL for toxicity to reproduction is higher than for repeated-dose toxicity.

VII. DNEL local (general population)

Basis for delineation of the DNELs local (long and short term toxicity):

Skin irritation:

500 mg Cohedur RK (= m-phenylene di(acetate)) were semiocclusively applied once to the intact skin (ear) of two young adult New Zealand white rabbits (3.0–4.0 kg) for an exposure period of 24 hours. Evaluation of skin irritation was made until day 7 according to Draize. Erythema and edema score was 0 at 24/48/72 hours.

In an additional in vitro skin irritation test using a human skin model, Resorcinol diacetate was non-irritant.

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is not justified.

Eye irritation:

A dose of 50 mg Chohedur RK (= m-phenylene di(acetate)) was administered into one eye of two young adult New Zealand white rabbits (3–4 kg). The eyes were examined and the grade of ocular reaction was recorded until day 7 post administration according to Draize. The cornea score was 2.66, the iris score was 0.83 and the conjunctivae and chemosis score were 2.33 and 1.33, respectively. All effects were reversible within 7 days. According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification as Eye Irrit. 2 ( H319: Causes serious eye irritation) is justified.

Sensitization

The results of the LLNA show that the test substance elicits a SI ≥ 3. An estimated EC3 value of 21.0% was calculated.

According to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments), Resorcinol diacetate should be classified as skin

sensitizer (Category 1B) and labeled as H317: May cause an allergic skin reaction.

Conclusion on local DNEL:

For local effects:

Low hazard band for Eye Irrit. 2 ( H319: Causes serious eye irritation).

Moderate hazard band for Skin sensitizer (Category 1B) (H317: May cause an allergic skin reaction).