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Description of key information

DEHP induced minimal skin and eye irritation in animals and did not induce skin irritation in human volunteers. Data are insufficient to determine the

respiratory irritant potential of DEHP.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
other: Little White Russian
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach
- Age at study initiation: no data
- Weight at study initiation: 2.1-2.3 kg
- Housing: individually
- Diet (e.g. ad libitum): ad libitum K4 diet for rabbits, Ssniff Spzialdiät GmbH, 4770 Soest
- Water (e.g. ad libitum): ad libitum tap water
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/-1
- Humidity (%): 60+/-5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
other: clipped (10x10cm)
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 h
Observation period:
8 d
Number of animals:
3 males
Details on study design:
The exposed skin area is 6 cm2.
After the 4-hour exposure, the exposed area was rinsed with warm water.
The skin reactions were evaluated after 1, 24, 48, and 72 hours, and after 6 and 8 days, using the grading system of the OECD guideline.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48, 72h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8d
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48, 72h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 8d
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48, 72h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8d
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48, 72h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48, 72h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48h
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48, 72h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48h
Irritant / corrosive response data:
At the 1-hour observation, all rabbits showed very slight erythema, and one rabbit also a very slight oedema. At 24 hours, the reaction of one rabbit had progressed to a well-defined erythema.
At 48 hours, all rabbits had very slight erythema which at 72 hours was accompanied by a dry appearance of the skin.
At 6 days, the skin surface appeared scaly, and at 8 days the skin was free from reaction.

Animal Number Sex 1h 24h 48 h 72 h 6 days 8 days
Erythema Oedema Erythema Oedema Erythema Oedema Erythema Oedema Erythema Oedema Erythema Oedema
1 38219 M 1 1 1 0 1 0 dryness 0 scaly 0 0
2 38335 M 1 0 2 1 1 0 dryness 0 scaly 0 0
3 38599 M 1 0 1 1 1 0 dryness 0 scaly 0 0
Interpretation of results:
slightly irritating
Remarks:
Migrated information not classified Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008
Conclusions:
DEHP was slightly irritating to the skin
Executive summary:

In a study performed in accordance with OECD guideline 404, skin irritation of DEHP (> 99% pure) was studied. The hair was clipped from the dorsal and lateral part of the trunk of three male Little White Russian rabbits. The undiluted test substance (0.5 cm2) was applied to a skin area of 6 cm2 and covered with a patch. After 4 hours, the patch was removed and the skin gently rinsed with warm water. The skin reactions were evaluated after 1, 24, 48, and 72 hours, and after 6 and 8 days, using the grading system of the OECD guideline. At the 1-hour observation, all rabbits showed very slight erythema, and one rabbit also a very slight oedema. At 24 hours, the reaction of one rabbit had progressed to a well-defined erythema. At 48 hours, all rabbits had very slight erythema which at 72 hours was accompanied by a dry appearance of the skin. At 6 days, the skin surface appeared scaly, and at 8 days the skin was free from reaction. It was concluded that DEHP was slightly irritating to the skin.

Mean scores calculated for times 24, 48 and 72h of animals 1, 2 and 3 were 1, 1.33 and 1 for erythema and 0, 0.33 and 0.33 for oedema, respectively.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The acute dermal irritative and corrosive properties of DEHP have been investigated in a study conforming with OECD guideline 404 (Mürmann, 1987). The hair was clipped from the dorsal and lateral part of the trunk of three male Little White Russian rabbits. Undiluted DEHP (> 99% pure) (0.5 ml) was applied to a skin area of 6 cm2and covered with a patch. After 4 hours, the patch was removed and the skin gently rinsed with warm water. The skin reactions were evaluated after 1, 24, 48, and 72 hours, and after 6 and 8 days, using the grading system of the OECD guideline. At the 1-hour observation, all rabbits showed very slight erythema, and one rabbit also a very slight oedema. At 24 hours, the reaction of one rabbit had progressed to a well-defined erythema. At 48 hours, all rabbits had very slight erythema which at 72 hours was accompanied by a dry appearance of the skin. At 6 days, the skin surface appeared scaly, and at 8 days the skin was free from reaction. It was concluded that DEHP was slightly irritating to the skin.

Mean scores calculated for times 24, 48 and 72h of animals 1, 2 and 3 were 1, 1.33 and 1 for erythema and 0, 0.33 and 0.33 for oedema, respectively.

In a skin irritation study performed according to GLP principles and conforming with the U.S. Food and Drug Administration (FDA) recommended method, 3 male and 3 female New Zealand White rabbits were used (Greenough, 1981). The skin of the back was clipped free of hair and 2 of the 4 patch test areas were abraded. One square inch chromatography paper patches were wetted with the undiluted test substance (DEHP), or with 10% aqueous sodium lauryl sulphate (as positive control substance). Patches were applied to both intact and abraded skin and left in position for 24 hours, thereafter the skin was cleansed. The test sites were scored immediately (24-hour reading) and 48 hours later (72-hour reading). Reactions were evaluated according to the FDA recommended scoring system. DEHP caused mild to moderate reactions at 24 hours. At the 72-hour reading, no treated sites showed any response to treatment.

Mean scores calculated for times 24 and 72h of the 6 treated animals (non-abraded) were 0.33 and 0.25 for erythema and for oedema, respectively. After abrasion of the skin, these scores were 0.58 and 0.5 for erythema and oedema, respectively.

Eye irritation

In another study also performed in accordance with OECD guideline 405, eye irritation of DEHP (>99% pure) was studied (Mürmann, 1987). DEHP in a volume of 0.1 ml was installed in the right eye of three male Little White Russian rabbits. The left eye served as control. The animals were evaluated after 1, 24, 48, and 72 hours, and after 6 days of application, using the grading system of the OECD guideline. At 1 hour, the conjunctivae of all three rabbits showed mild redness and one rabbit showed mild discharge. No conjunctival reactions were observed at the later observation times. All observations for chemosis, corneal opacity and lesions of the iris were negative. Mean irritation scores calculated for times 24, 48 and 72h of the animals 1, 2, 3 were 0, 0, 0 for cornea, 0, 0, 0 for iris, 0, 0, 0 for conjunctiva and 0, 0, 0 for chemosis, respecitvely.

In a study performed according to GLP principles and conforming with the U.S. Food and Drug Administration (FDA) recommended method, DEHP in a volume of 0.1 ml was introduced into the right eye of 3 male and 3 female New Zealand White rabbits (Greenough, 1981). The eyes were examined at 1, 24, 48, and 72 hours, and at 7 days, and the reactions were scored according to the FDA recommended scoring system. No reactions were found in the cornea or iris at any point of time. The conjunctivae of 5 eyes exhibited mild redness at 1 hour, while one eye showed very mild redness. At 24 hours, mild redness persisted in 3 eyes, while the remainder had no redness. No redness was observed at 72 hours or 7 days.

Mean irritation scores calculated for times 24, 48 and 72h of the 6 treated animals were 0 for cornea, 0 for iris, 0.14 for conjunctiva and 0.14 for chemosis.

Respiratory tract irritation

No studies specifically addressing this issue have been found.

In a study of acute toxicity by inhalation, groups of rats were exposed to DEHP in concentrations of 3.39, 6.82 or 10.62 mg/litre for 4 hours (Greenough, 1981). The respiratory tract was subjected to detailed macroscopic examination in all animals and revealed dark red foci and patches in the lungs. These foci and patches were observed more frequently in the treated animals (present in 19 out of 30 rats exposed to DEHP) than in the controls (present in 2 out of 10 rats exposed to clean air). The lung-to-body weight ratios of all treated groups were similar to the ratios obtained in the control group.

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

According to the criteria edicted in REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008, no classification is warranted for skin, eye and respiratory irritation.