Registration Dossier

Administrative data

Description of key information

Skin:
Overall, topically applied 1,2-dichloroethane produced no or only slight irritation to skin. Nevertheless, the substance was classified as irritating to the skin.
Eye:
Overall, instilled 1,2-dichloroethane produced no or only slight to transiently moderate irritation to eyes. Nevertheless, the substance was classified as irritating to the eyes.
Respiratory system:
Based on respiratory irritating and tissue damaging potential (inhalation studies) a classification and labeling STOT SE cat. 3 as given in Annex VI in CLP regulation (1272/2008/EC) is justified.

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:
weight of evidence
Study period:
1976
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Early standard study, very limited documentation, exposure regimen fails to allow interpretation on the basis of current standards (4-h exposure).
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
Principles of method if other than guideline:
Acc. to Draize (described in Duprat et al., 1974)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
- Sex: female
- Weight at study initiation: 2.4-3.0 kg
Type of coverage:
occlusive
Preparation of test site:
other: scarified and intact skin
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
undiluted
Duration of treatment / exposure:
24 hours
Observation period:
no data
Number of animals:
30 animals
Details on study design:
Comparative study including various chlorinated solvents: Dermal application of 0.5 mL under occluded conditions on the scarified and intact skin. Skin was histologically examined on day 3 post-exposure.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 72 h
Score:
4.7
Max. score:
8
Irritant / corrosive response data:
Only overall rating was given (by primary irritation index), but effects specified could not be exactly allocated to the individual test substance. An appraisal was not possible but through comparison relative to the findings on the other substances involved.  For example, chloroform and perchloroethylene were graded as "severe" irritants (PI = 5.6 and 6.1, resp., of max. 8 scores), tetrachloromethane was assigned "moderate" (PI = 4.2).
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Remarks:
Migrated information
Conclusions:
A primary irritation index of 4.7 was measured for skin irritation of 1,2-dichloroethane in rabbits. According to CLP Regulation (1272/2008/EC) the substance was classified as irritant (GHS, cat. 2).
Executive summary:

In a primary dermal irritation study, New Zealand White rabbits (6 females) were dermally exposed to 0.5 mL of undiluted 1,2-dichloroethane for 4 hours. Animals then were observed for at least 3 days. Irritation was scored by the method of Draize. A primary irritation index of 4.7 was measured for skin irritation of 1,2-dichloroethane. According to CLP Regulation (1272/2008/EC) the substance was classified as irritant (GHS, cat. 2).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation:

1,2-dichloroethane failed to produce any signs of irritation when applied to the skin of 6 rabbits in an early skin irritation test which, however, has been conducted according to current standards (occluded 4-h exposure, intact skin, acc. to FDA Rev., Fed. Reg. 37, No. 244, 1972, USA) (Stauffer Chemical, 1973).

A second test revealed moderate irritation on the intact and scarified skin of rabbits (primary irritation index 4.7 of max. 8 scores), but the test design and conditions apparently corresponded to the genuine Draize assay using occluded 24-h exposure (Duprat et al., 1976).

A third non-standard test on skin of guinea pigs treated with 1 ml of the neat material for up to 16 hours under occluded conditions (cover-glass limited skin area approx. 3.1 cm²) produced mild signs of irritation after 4- and 16-hour exposure, but none after 15 or 60 minutes. Effects were microscopically characterized as slight degenerative changes in the epidermis, slight focal karyopyknosis, slight perinuclear oedema in the region of cells with pyknotic nuclei, spongiosis and junctional separation (Kronevi et al., 1981). This test design did not allow to correlate the microscopically identified changes with those classical, macroscopic indicators for irritation which are common under the current classification system.

Eye irritation:

The eye irritating properties of 1,2-dichloroethane were investigated in rabbits, dogs and guinea pigs. Rabbits were administered 0.1 ml of the pure substance into the conjunctival sac. Moderate lacrimation, abrasion of the corneal epithelium and mild to moderate catarrhal conjunctivae were observed. In addition, regenerating keratitis was evident on day 7 which disappeared after another seven days. In this study, the substance was judged to be slightly irritating, based on an overall Draize-score ranking with 7 of max. 110 scores (Duprat et al., 1976).

In another rabbit study, 0.1 ml of the neat material was applied into the conjunctival sac. Slight reddening and annular conjunctival swelling were noted in 2/6 and 1/6 animals, respectively. All symptoms disappeared completely within three days (Stauffer Chemical, 1973).

After single inhalation exposure to 1000 or 1500 ppm (4110 and 6165 mg/m³) of 1,2-dichloroethane for 7 h, dogs experienced corneal turbidity and oedema, an effect not found in other species tested but a fox (among them cats, monkeys, rabbits, chickens and various rodents) (Heppel et al., 1944): At a concentration of 1000 ppm, symmetric turbidity of the corneas was observed in 8/10 dogs, while at the toxic concentration of 1500 ppm, 1/6 dogs showed corneal damage, 1/6 developed faint turbidity and 4/6 showed intense clouding of both corneas which cleared within one week in one animal. Resistance to the cornea effects of 1,2 -dichloroethane developed and remained unchanged even after cessation of exposure for two to four weeks. Prolonged exposure to 400 ppm (about 1600 mg/m³) for 25 weeks gave no evidence of eye damage, whereas during exposure to the toxic concentration of 1000 ppm (4110 mg/m³) corneal opacity was prominent (Heppel et al., 1946).

Guinea pigs were exposed to concentrations of 600 to about 70000 ppm (2500 to about 29,000 mg/m³) of 1,2-dichloroethane. Eye and nose irritation (squinting and lacrimation), occurred after exposure to toxic concentrations of 2000-4000 ppm within less than 10 min. No signs of irritation and intoxication, but occasional retching in 1/18 animals were reported at 1200 ppm (approx. 5000 mg/m³) after exposure for several hours (Sayer et al., 1930).

Conclusion:

Overall, instilled 1,2-dichloroethane produced no or only slight to transiently moderate irritation to eyes. Other assays using atmospheric exposure suggested that significant irritancy or locally noxious effects only emerged at concentrations which already produced other systemic intoxication:

1. The species-specific effect on the eye of dogs following atmospheric exposure was not observed during exposure to 400 ppm for up to 25 weeks. This concentration was distinctly higher than for general systemic intoxication after prolonged exposure to 1,2-dichloroethane.

2. The clinical rather than pathologically relevant irritation reflexes in guinea pigs noted during 8 -h exposure to 1200 ppm atmospheric 1,2- dichloroethane could be appropriate to set an acute irritation threshold concentration. Also this concentration clearly fell within or above the range of acute toxicity (Spencer et al., 1951).

Respiratory irritation:

Based on respriatory irritating and tissue damaging potential (inhalation studies) a classification and labelling STOT SE cat. 3 as given in Annex VI in CLP (Regulation 1272/2008/EC) is justified.


Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Effects on respiratory irritation: irritating

Justification for classification or non-classification

The susbtance is subject to harmonised classification and labelling according to Annex VI of CLP regulation 1272/2008/EC.

Skin irritation:

Overall, topically applied 1,2 -dichloroethane produced no or only slight irritation to skin. In CLP Regulation (1272/2008/EC) Annex VI a classification as skin irritant (Xi, R38 Irritating to the skin) according to Directive 67/548/EEC and skin irritating cat. 2 (H315 Causes skin irritation) is included.

Eye irritation:

Overall, instilled 1,2 -dichloroethane produced no or only slight to transiently moderate irritation to eyes. In CLP Regulation (1272/2008/EC) Annex VI a classification as eye irritant (Xi, R36 Irritant; Risk of serious damage to eyes) according to Directive 67/548/EEC and eye irritating cat. 2 (H319 Causes serious eye irritation) is included.

Respiratory irritation:

Based on respiratory irritating and tissue damaging potential (inhalation studies) a classification and labelling STOT SE cat. 3 (H335 May cause respiratory irritation) according to Regulation 1272/2008/EC and irritant to respiratory system (Xi, R 37 Irritating to respiratory system) according to Directive 67/548/EEC as given in Annex VI in CLP is justified.