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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 - 31 March 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in 1978 before the introduction of GLP and OECD methodology.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report date:
1978

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Hagan EC (1959) Acute toxicity in Appraisal of the Safety of chemicals in foods, drugs and cosmetics, pp 17-25
Principles of method if other than guideline:
Four groups of 3male and 3 female albino rats were given doses of 1.0, 2.0, 5.0 and 10.0 ml/kg, applied to the shaved mildly abraded skin under an occlusive patch for 24 h then observed for 14 days. The DEP was used as received. Animals were observed for signs of pharmacologic activity and toxicity 1, 3, 6 and 24 hours post application and daily thereafter for a total of 14 days. Animals sacrificed at the end of the 14 day observation period were subjected to a complete gross necropsy.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Diethyl phthalate
EC Number:
201-550-6
EC Name:
Diethyl phthalate
Cas Number:
84-66-2
Molecular formula:
C12H14O4
IUPAC Name:
.
Details on test material:
- Name of test material (as cited in study report): 78-033-2 - Identified as diethyl phthalate (DEP
- Physical state: liquid
- Analytical purity: Not reported
- Lot/batch No.: Not reported

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Summit View Farm, Belvidere, New Jersey, USA
- Age at study initiation: Not reported
- Weight at study initiation: Males: 140 - 170g; females: 154 - 178g
- Fasting period before study: no
- Housing: standard laboratory conditions
- Diet (e.g. ad libitum): Wayne animal feed
- Water (e.g. ad libitum): yes
- Acclimation period: yes, period not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): standard laboratory conditions
- Humidity (%): standard laboratory conditions
- Air changes (per hr): standard laboratory conditions
- Photoperiod (hrs dark / hrs light): standard laboratory conditions

IN-LIFE DATES: From: 16 March To: 31 March 1978

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Not reported
- % coverage: 10
- Type of wrap if used: gauze patches covered by an impermeable plastic wrapping

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: immediately

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.0, 2.0, 5.0 or 10 ml/kg
- Concentration (if solution): 100% as supplied
- Constant volume or concentration used: no
- For solids, paste formed: yes/no

VEHICLE
- Amount(s) applied (volume or weight with unit): N/A
- Concentration (if solution): N/A
- Lot/batch no. (if required): N/A
- Purity: N/A
Duration of exposure:
24 hours
Doses:
1.0, 2.0, 5.0 or 10 mL/kg
No. of animals per sex per dose:
3 males and 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs - 1, 3, 6 and 24 hours following dosing and daily thereafter for a total of 14 days. Body weight recorded at initiation and termination.
- Necropsy of survivors performed: yes
Statistics:
Not required as there were no deaths and an LD 50 could not be calculated.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 mL/kg bw
Based on:
test mat.
Mortality:
None in any dose group.
Clinical signs:
Skin slightly reddened in all animals when dressings removed
Body weight:
No definite effects in male rats and no effects in female rats.
Gross pathology:
No abnormalitities detected
Other findings:
None reported

Any other information on results incl. tables

LD50 > 10 ml/kg

Dose Level              Sex              Dead/dosed              % Mortality

(ml/kg)                      M:F

1.0                            3:3                    0/3:0/3                     0:0

2.0                            3:3                     0/3:0/3                     0:0

5.0                            3:3                     0/3:0/3                     0:0

10.0                         3:3                      0/3:0/3                     0:0

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 > 10 ml/kg
Executive summary:

Acute toxicity following administration of a single dermal dose over a 24 hour period has been investigated in the rat. The LD50 was determined to be in excess of 10 mL/kg body weight. This equates to a dose level of 11181 mg/kg when corrected for density.