Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: TRGS 900
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEC
Value:
62.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
No repeated dose inhalation study available
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
No time extrapolation is conducted, as the NOAEL in a 10 day study in the same rat strain is identical with the NOAEL of a 90 day study (see justification for 1,3-dichlorobenzene in TRGS 900
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:
1
Justification:
Since the NOAEL was derived in respect to thyroid changes in rats, which are considered to be more sensitive to thyroid changes than humans, no additional factor is justified
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:
DNEL (Derived No Effect Level)
Value:
24 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: TRGS 900
DNEL extrapolated from long term DNEL

Local effects

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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.85 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):
20
Modified dose descriptor starting point:
NOAEL
Value:
37 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No repeated dermal toxicity study available
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
No time extrapolation is conducted, as the NOAEL in a 10 day study in the same rat strain is identical with the NOAEL of a 90 day study (see justification for 1,3-dichlorobenzene in TRGS 900
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (ECHA) for rat versus human
AF for other interspecies differences:
1
Justification:
Since the NOAEL was derived in respect to thyroid changes in rats, which are considered to be more sensitive to thyroid changes than humans, no additional factor is justified
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:
DNEL (Derived No Effect Level)
Value:
3.7 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

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)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

1,3-dichlorobenzene

(CAS 541-73-1)

DNELs (worker)

I. Introduction:

Classification

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

Acute Tox.4*; H302

Self-classification: Acute Tox.4; H302, Skin Irrit.2; H315, Skin Sens.1B; H317

Known occupational exposure limit(s):

SCOEL: no data

TRGS 900: 2 ppm (= 12 mg/m³); exceeding factor: 2

MAK: 2 ppm (= 12 mg/m³); exceeding factor: 2

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 band 1.85 mg/kg bw/day

Dermal (short term) moderate hazard band 3.70 mg/kg bw

Inhalation (long term) moderate hazard band 12 mg/m³ per day

Inhalation (short term) moderate hazard band 24 mg/m³

Hazard for eyes 1,3-dichlorobenzene is not classified as irritant to the eyes

III. DNEL systemic (worker)

Basis for delineation of the DNELs systemic:

According to ECHA Guidance Document R.8; Appendix R 8-13 (Version 2.1, November 2012) a national Occupational Exposure Limit (OEL) can be used in place of a DNEL under certain circumstances.

In the TRGS 900 (Technical Rule for Hazardous Substances 900) established by the German Federal Institute for Occupational Safety and Health (BAuA) the legally binding occupational exposure values for 1,3-dichlorobenzene are 2 ppm (=12 mg/m³) with an exceeding factor of 2 (Peak limitation); TRGS900 (2015).

The values of the TRGS 900 are based on a comprehensive opinion by the MAK Commission (MAK 2008; Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area) and published in the List of MAK and BAT Values 2014: Maximum Concentrations and Biological Tolerance Values at the Workplace.

The justification of the OEL of 2 ppm (=12 mg/m³) in the TRGS 900 is as follows (translated from the justification in German language; TRGS900, 2015):

The occupational medical and toxicological data on 1,3-dichlorobenzene are summarized in the MAK supplement of 1.3-dichlorobenzene (MAK 2008). After the application of 1,3-dichlorobenzene by gavage over 90 days in male and female Sprague-Dawley rats at a dose of 147 mg/kg bw/day and higher increased relative liver and kidney weights occurred and in male rats a vacuolization in cells of the pars distalis in the pituitary glands were observed (McCauley et al. 1995).

According to the MAK justification comparable changes in the pituitary gland are observed in castrated or old rats with testicular atrophy. From 37 mg kg bw/day, a decrease in colloid density was found in the thyroid follicles, which is not considered relevant to humans.

Therefore, a NOAEL of 37 mg/kg bw/day is taken as the starting point for the derivation of the OEL.

Using an allometric scaling factor 4 for the basal metabolic rate and a default factor of 5 to account for the inter- and intra-species variability resulted in an OEL of 2 ppm (12 mg/m³).

This value is identical to the MAK-value for 1,3-dichlorobenzene.

A time extrapolation is not performed because in a 10-day oral study in Sprague-Dawley rats also a NOAEL of 37 mg/kg bw/day was determined (McCauley et al., 1995).

Higher doses resulted in increased relative liver and kidney weights and caused hepatocellular degeneration. Since the critical effect is of systemic nature and no substance-specific data are available an exceeding factor 2 of the Category II is defined as peak limit.

In a developmental toxicity study with 1,3-dichlorobenzene in rats up to the highest tested dose of 200 mg/kg bw/day no developmental toxic effects were described (Ruddick et al., 1983).

Study

Title:

Toxicity studies of 1,3-dichloro-benzene in Sprague-Dawley rats

Administration period:

90-day oral (gavage) sub-chronic toxicity study in the rat

Doses:

rat: 0 (control), 9, 37, 147 or 588 mg/kg bw/day via gavage (daily).

NOAEL

NOAEL = 37 mg/kg bw/day

Effects

Based on the following effects:

Increased incidence of thyroid changes in the form of a decreased colloid density in the thyroid follicles which are not regarded as relevant for humans.

Reference

McCauley PT, Robinson M, Daniel FB, and Olson GR. Toxicity studies of 1,3-dichlorobenzene in Sprague-Dawley rats

Drug & Chem. Toxicol. 18, 201-221 (1995)

Long-term toxicity – systemic effects (worker)

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

NOAEL(oral) = 37 mg/kg bw/day

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

Corrected inhalatory NOAEC = Oral NOAEL (37 mg/kg) x 1/0.38 m³/kg x 6.7 m³/10m³ x 1

=> NOAEC worker = 65.2 mg/m³

Factors to be applied                                          Justification

AF for dose response relationship 1

AF for differences in duration of exposure 1       No time extrapolation is conducted, as the NOAEL in a 10 day study in the same rat strain is identical with the NOAEL of a 90 day study (see justification for 1,3-dichlorobenzene in TRGS 900

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 5                    Default value (ECHA) for worker

AF for other interspecies differences 1            Since the NOAEL was derived in respect to thyroid changes in rats, which are considered to be more sensitive to thyroid changes than humans, no additional factor is justified.

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 5

Worker DNEL long-term for inhalation route - systemic 13.0 mg/m³ (12 mg/m³ according TRGS 900)

In the 28 day study rats were exposed daily, whereas workers are exposed for 5 days a week. In accordance with the DNEL derivation in the TRGS 900 Justification for 1,3diclorobenzene a correction factor of 1.4 is omitted.

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

An exceeding factor of 2 is used.

Therefore:

Worker DNEL short-term for inhalation exposure: 26.0 mg/m³ (24 mg/m³ according TRGS 900)

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

NOAEL(oral) = NOAEL(dermal) = 37 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 1

AF for differences in duration of exposure 1       No time extrapolation is conducted, as the NOAEL in a 10 day study in the same rat strain is identical with the NOAEL of a 90 day study (see justification for 1,3-dichlorobenzene in TRGS 900

AF for interspecies differences 4                      Default value (ECHA) for rat versus human

AF for intraspecies differences 5                      Default value (ECHA) for worker

AF for other interspecies differences 1               based on Justification for 1,3-dichlorobenzene in TRGS 900

AF for quality of the whole database 1               Since the NOAEL was derived in respect to thyroid changes in rats, which are considered to be more sensitive to thyroid changes than humans, no additional factor is justified.

AF for remaining differences 1

Overall factor 20

worker DNEL long term for oral and dermal route - systemic: 1.85 mg/kg bw/day

In the 28 day study rats were exposed daily, whereas workers are exposed for 5 days a week. In accordance with the DNEL derivation in the TRGS 900 Justification for 1,3diclorobenzene a correction factor of 1.4 is omitted.

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

An exceeding factor of 2 is used.

Therefore:

Worker DNEL short-term for oral and dermal exposure: 3.70 mg/kg bw

Reproductive Toxicity – systemic effects (worker)

In the 90 day repeated dose systemic toxicity study, a gross and histopathological examination was performed on all major organs inclusive reproductive organs/tissues (gonads, seminal vesicles, prostate, preputial or clitoral gland). No relevant adverse effects on reproductive tissues/organs were detected at the highest applied dose (588 mg/kg bw/d).

In a teratogenicity study, 1,3-dichlorobenzene was administered by gavage to pregnant Sprague-Dawley rats on their 6th - 15th day of gestation. Dosages were 50, 100 or 200 mg/kg bw/day. Maternal weight gain, changes in microscopic examination and 15 biochemical parameters were used to evaluate maternal toxicity. Fetal changes were measured by litter size, fetal weight, deciduoma, skeleton and visceral examination, residue analysis and microscopy.1,3-dichlorobenzene revealed no teratogenic effects.

Since no potential fertility effects are observed at 588 mg/kg bw/day only and no teratogenic effects are observed at 200 mg/kg bw/day (in each study the highest applied dose), the DNEL (systemic) of 1.85 mg/kg bw/day is regarded to be protective for potential fertility and teratogenic effects.

VII. DNEL local (worker)

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

Irritation/corrosion

In the key study 1,3-dichlorobenzene was irritating to the skin. According to EU-GHS regulation a classification as Skin Irrit. Cat 2, H315 (causes skin irritation) is justified.

The test substance was slightly irritating to the eye, but the measured score values were not sufficient for classification.

Sensitization

A modified Local Lymph Node Assay (IMDS) was performed on 24 female NMRI mice of the strain Hsd Win:NMRI (6 animals/test item group and 6 control animals) to determine if there is any specific (sensitizing) or non-specific (irritant) stimulating potential of the test item m-dichlorobenzene. The EC 1.4 value calculated is 26.30% for this test item. In accordance with the classification proposed in the Technical Report No. 78 of the ECETOC this value corresponds to a weak skin sensitizer.

Therefore a classification as Skin Sens 1B; H317 is justified.

Conclusion on local DNEL:

For local effects the derivation of a long-term DNEL for dermal toxicity is not appropriate due to the skin irritation and skin sensitization.

Based on the classification as Skin Irrit. Cat 2; H315, 1,3-dichlorobenzene should be allocated to the low hazard band. Due to the classification as Skin Sens 1B; H317, 1,3-dichlorobenzene should be allocated to the moderate hazard band. Overall, the allocation of 1,3-dichlorobenzene to the moderate hazard band is justified for local dermal effects and the allocation to the low hazard band is justified for inhalation effects.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.21 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: TRGS 900
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Value:
32.17 mg/m³
Explanation for the modification of the dose descriptor starting point:
No repeated dose inhalation toxicity study available
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
No time extrapolation is conducted, as the NOAEL in a 10 day study in the same rat strain is identical with the NOAEL of a 90 day study (see justification for 1,3-dichlorobenzene in TRGS 900
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:
1
Justification:
Since the NOAEL was derived in respect to thyroid changes in rats, which are considered to be more sensitive to thyroid changes than humans, no additional factor is justified.
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:
DNEL (Derived No Effect Level)
Value:
6.42 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: TRGS 900
DNEL extrapolated from long term DNEL

Local effects

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

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.92 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):
40
Modified dose descriptor starting point:
NOAEL
Value:
37 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No repeated dose dermal toxicity study available
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
No time extrapolation is conducted, as the NOAEL in a 10 day study in the same rat strain is identical with the NOAEL of a 90 day study (see justification for 1,3-dichlorobenzene in TRGS 900
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (ECHA) for rat versus human
AF for other interspecies differences:
1
Justification:
Since the NOAEL was derived in respect to thyroid changes in rats, which are considered to be more sensitive to thyroid changes than humans, no additional factor is justified.
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:
DNEL (Derived No Effect Level)
Value:
1.84 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

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)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.92 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: TRGS 900
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
37 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
No time extrapolation is conducted, as the NOAEL in a 10 day study in the same rat strain is identical with the NOAEL of a 90 day study (see justification for 1,3-dichlorobenzene in TRGS 900
AF for interspecies differences (allometric scaling):
4
Justification:
Default value (ECHA) for rat versus human
AF for other interspecies differences:
1
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are performed according to guideline and GLP.
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:
DNEL (Derived No Effect Level)
Value:
1.84 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

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) not required 0.92 mg/kg bw/day

Oral (short term) not required 1.84 mg/kg bw

Dermal (long term) moderate hazard band 0.92 mg/kg bw/day

Dermal (short term) moderate hazard band 1.84 mg/kg bw

Inhalation (long term) moderate hazard band 3.21 mg/m³ per day

Inhalation (short term) moderate hazard band 6.42 mg/m³

Hazard for eyes 1,3-dichlorobenzene is not classified as irritant to the eyes

VI. DNEL systemic (general population)

Basis for delineation of the DNELs systemic:

Male and female Sprague-Dawley rats received 1,3-dichlorobenzene ( 0, 9, 37, 147 and 588 mg/kg bw) daily by corn oil gavage for 90 days (method similar to OECD guideline 408). The NOAEL = 37 mg/kg bw/day based on increased incidence of thyroid changes in the form of a decreased colloid density in the thyroid follicles which are not regarded as relevant for humans.

Long-term toxicity – systemic effects (general population)

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

NOAEL(oral) = 37 mg/kg bw/day

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

Corrected inhalatory NOAEC = Oral NOAEL (37 mg/kg) x 1/1.15 m³/kg x 1.0

=> NOAEC general population = 32.17 mg/m³

Factors to be applied                                                 Justification

AF for dose response relationship 1

AF for differences in duration of exposure 1       No time extrapolation is conducted, as the NOAEL in a 10 day study in the same rat strain is identical with the NOAEL of a 90 day study (see justification for 1,3-dichlorobenzene in TRGS 900

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 1 Since the NOAEL was derived in respect to thyroid changes in rats, which are considered to be more sensitive to thyroid changes than humans, no additional factor is justified.

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 10

General population DNEL long-term for inhalation route - systemic: 3.21 mg/m³

1,3-dichorobenzene has a water solubility of 120 mg/L (25°C) and a log Pow of 3.53 (22°C). 1,3-dichlorobenzene is readily absorbed after ingestion (MAK 2013). Following oral administration of a dose of 200 mg/bw, 1,3-dichlorobenzene in rats the maximum blood levels was achieved within 30 minutes. Within the following 12 hours, there was a biphasic decline in concentration in the blood (half-life =4.4 hour). Therefore no factor is used for route-to-route extrapolation and oral absorption is assumed to be similar to inhalation absorption.

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

An exceeding factor of 2 is used.

Therefore:

General population DNEL short-term for inhalation exposure: 6.42 mg/m³

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

NOAEL(oral) = NOAEL(dermal) = 37 mg/kg bw/day

Factors to be applied                                                  Justification

AF for dose response relationship 1

AF for differences in duration of exposure 1        No time extrapolation is conducted, as the NOAEL in a 10 day study in the same rat strain is identical with the NOAEL of a 90 day study (see justification for 1,3-dichlorobenzene in TRGS 900

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 1               based on Justification for 1,3-dichlorobenzene in TRGS 900

AF for quality of the whole database 1               Since the NOAEL was derived in respect to thyroid changes in rats, which are considered to be more sensitive to thyroid changes than humans, no additional factor is justified.

AF for remaining differences 1

Overall factor 40

General population DNEL long term for oral and dermal route - systemic: 0.92 mg/kg bw/day

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

An exceeding factor of 2 is used.

Therefore:

General population DNEL short-term for oral and dermal exposure: 1.84 mg/kg bw

Reproductive Toxicity – systemic effects (general population)

In the 90 day repeated dose systemic toxicity study, a gross and histopathological examination was performed on all major organs inclusive reproductive organs/tissues (gonads, seminal vesicles, prostate, preputial or clitoral gland). No relevant adverse effects on reproductive tissues/organs were detected at the highest applied dose (588 mg/kg bw/d).

In a teratogenicity study, 1,3-dichlorobenzene was administered by gavage to pregnant Sprague-Dawley rats on their 6th - 15th day of gestation. Dosages were 50, 100 or 200 mg/kg bw/day. Maternal weight gain, changes in microscopic examination and 15 biochemical parameters were used to evaluate maternal toxicity. Fetal changes were measured by litter size, fetal weight, deciduoma, skeleton and visceral examination, residue analysis and microscopy.1,3-dichlorobenzene revealed no teratogenic effects.

Since no potential fertility effects are observed at 588 mg/kg bw/day only and no teratogenic effects are observed at 200 mg/kg bw/day (in each study the highest applied dose), the DNEL (systemic) of 0.92 mg/kg bw/day is regarded to be protective for potential fertility and teratogenic effects.

VII. DNEL local (general population)

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

Irritation/corrosion

In the key study 1,3-dichlorobenzene was irritating to the skin. According to EU-GHS regulation a classification as Skin Irrit. Cat 2, H315 (causes skin irritation) is justified.

The test substance was slightly irritating to the eye, but the measured score values were not sufficient for classification.

Sensitization

A modified Local Lymph Node Assay (IMDS) was performed on 24 female NMRI mice of the strain Hsd Win:NMRI (6 animals/test item group and 6 control animals) to determine if there is any specific (sensitizing) or non-specific (irritant) stimulating potential of the test item m-dichlorobenzene. The EC 1.4 value calculated is 26.30% for this test item. In accordance with the classification proposed in the Technical Report No. 78 of the ECETOC this value corresponds to a weak skin sensitizer.

Therefore a classification as Skin Sens 1B; H317 is justified.

Conclusion on local DNEL:

For local effects the derivation of a long-term DNEL for dermal toxicity is not appropriate due to the skin irritation and skin sensitization.

Based on the classification as Skin Irrit. Cat 2; H315, 1,3-dichlorobenzene should be allocated to the low hazard band. Due to the classification as Skin Sens 1B; H317, 1,3-dichlorobenzene should be allocated to the moderate hazard band.

Overall, the allocation of 1,3-dichlorobenzene to the moderate hazard band is justified for local dermal effects and the allocation to the low hazard band is justified for inhalation effects.