Diethyl phthalate

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1984

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Data from a preliminary study to select doses for a subsequent carcinogenicity study. Full range of parameters typical for repeat dose studies not examined

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

Unnamed

Year:

2001

Reference 2

Reference Type:

study report

Title:

Unnamed

Report date:

1995

Materials and methods

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

To evaluate the toxic effects of repeated exposure to DEP by the dermal route and to select suitable dose levels for use in subsequent 2 year studies

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

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): diethyl phthalate
- Physical state: liquid
- Analytical purity:>99%
- Stability under test conditions: 2 weeks
- Storage condition of test material: stored in amber glass bottles protected from light at room temperature
- Other: The stability of the bulk chemical was monitored periodically using GC. No degradation of the bulk chemical occurred.

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Simonsen Laboratories Inc Gilroy CA USA
- Age at study initiation: approximately 42 days
- Weight at study initiation: range of mean weights males: 20.6-21.4g; females: 15.9-16.5g
- Fasting period before study: N/A
- Housing: individual
- Diet (e.g. ad libitum): yes, NIH07 open formula meal (Zeigler Brothers, Gardeners PA USA
- Water (e.g. ad libitum): yes, by automatic system
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23-24 degrees C
- Humidity (%): 28-74%
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12h

IN-LIFE DATES: From: 1984-09-05 To: 1984-10-08

Administration / exposure

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Details on exposure:

TEST SITE
- Area of exposure: interscapular skin
- % coverage: not reported
- Type of wrap if used: N/A

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not reported
- Time after start of exposure: not reported

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0, 12.5, 25, 50 or 100ul
- Concentration (if solution): 100% used as supplied
- Constant volume or concentration used: yes/no: constant concentration
- For solids, paste formed: N/A

USE OF RESTRAINERS FOR PREVENTING INGESTION: no

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Periodic analyses using reverse phase HPLC

Duration of treatment / exposure:

Ca 4 weeks

Frequency of treatment:

5 times /w (Monday -Friday)

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 12.5, 25, 50 or 100ul
Basis:
nominal per unit area

No. of animals per sex per dose:

10 males & 10 females

Control animals:

yes, concurrent no treatment

Details on study design:

Animals randomly assigned to treatment groups using a computer generated randomisation procedure

Positive control:

No

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: 2 X daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: initially then weekly thereafter

DERMAL IRRITATION (if dermal study): No
- Time schedule for examinations:

BODY WEIGHT: Yes
- Time schedule for examinations: initially then weekly thereafter

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - complete histopathologic examinations conducted on all animals; Gross lesions, tissue masses and adrenal gland, brain, oesophagus, gall bladder , heart, kidney, lcolon, caecum, rectum, liver, lung, mammary gland, mandibular & mesenteric lymphnodes, nose, ovary, parathyroid gland, pituitary gland, prostate gland, salivary gland, seminal vesicles, skin ( site of application, control & other), duodenum, jejunum, ileum, spleen, sternum, stomach, testis, thymus, thyroid gland, trachea, urinary bladder & uterus

Other examinations:

No

Statistics:

Means & SDs & Williams or Dunnetts test

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

One female in the control group died. There were no clinical signs indicative of toxicity

Dermal irritation:

not examined

Mortality:

mortality observed, treatment-related

Description (incidence):

One female in the control group died. There were no clinical signs indicative of toxicity

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Final mean body weights of female mice given DEP were 5-7% heavier than controls

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Absolute & relative liver weights were greater in females given 25 & 100 ul DEP than in controls.

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Details on results:

CLINICAL SIGNS AND MORTALITY: No effect of treatment

BODY WEIGHT AND WEIGHT GAIN: No effect of treatment

FOOD CONSUMPTION: No effect of treatment

ORGAN WEIGHTS: Absolute & relative liver weights were greater in females given 25 & 100 ml DEP than in controls.

GROSS PATHOLOGY: No effect of treatment

HISTOPATHOLOGY: NON-NEOPLASTIC: No effect of treatment

OTHER FINDINGS: None

Effect levels

Dose descriptor:

NOAEL

Effect level:

12.5 other: ul

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Increased liver weight (absolute & relative) in mice given 25 and 100 ul DEP.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Under the conditions of this study DEP applied neat to the skin of mice 5/7 days for 28 days the only effect was an increase in liver weight (absolute & relative) in those given 25 & 100 ul/31 & 123 mg. The NOAEL is considered to be 12.5 ul (15 mg).

Executive summary:

Under the conditions of this study DEP applied neat to the skin of mice 5/7 days for 28 days the only effect was an increase in liver weight (absolute & relative) in those given 25 & 100 ul/31 & 123 mg. The NOAEL is considered to be 12.5 ul (15 mg).