Dimethyl phthalate

Endpoint summary

Description of key information

DMP is practically non-toxic after a single ingestion, after short-term inhalation and short-term skin contact.
Oral: LD50 = 8200 mg/kg bw (rat)
Dermal: LD50 > 12000 mg/kg bw (rabbit, occlusive)
Inhalation: LC0 = 10.4 mg/L (rat)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is sufficient for endpoint evaluation with acceptable restrictions due to limited reporting (non-GLP study).

Principles of method if other than guideline:

Method: other - "Acute oral toxicity" testing, animals were starved 18h prior to treatment (exept mice), administration of graded doses to groups of ten animals, recording of dosage-mortality curves (LD50 estimation)

GLP compliance:

no

Test type:

other: Acute oral toxicity according to Draize (1948)

Limit test:

yes

Specific details on test material used for the study:

IUCLID4 Test substance: other TS

TS-Freetext:
Dimethyl phthalate;
CAS-No.: 131-11-3;
no further data

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Fasting period before study: 18h

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

not reported

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 6 days
- Necropsy of survivors performed: no
- Other examinations performed: other: mortalities were recorded

Sex:

not specified

Dose descriptor:

LD50

Effect level:

8 200 mg/kg bw

Remarks on result:

other: Original data: LD50 = 6.9 ml/kg bw, density = 1.194 g/ml; Calculation: LD50 = 8200 mg/kg bw

Mortality:

mortality occured within 7h to 3days post application

Clinical signs:

other: - animals exhibited drowsiness and listlessness within 15min after application - high doses produced a state not unlike anesthesia

Conclusions:

LD50 in rat for oral gavage of 8200 mg/kg bw was determined (original data: LD50 = 6.9 ml/kg bw, density 1.194 g/ml).

Executive summary:

The study is sufficient for endpoint evaluation with acceptable restrictions due to limited reporting (non-GLP study). Dimethyl phtalate was tested in rats (undiluted test substance). Oral toxicity via gavage was tested with neat substance in rats. Mortalities occurred. Signs of intoxication in the rat included drowsiness within the first 15 min after an acute oral dose. Animals rapidly became semi-conscious, deaths occurred between 7 h and 3 days.

An LD50 in rat for oral gavage of 8200 mg/kg bw was determined (original data: LD50 = 6.9 ml/kg bw, density 1.194 g/ml).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

8 200 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study is not assignable. Only secondary literature and only short table available. However, reliable key studies with restrictions (non-GLP studies) are available for the first, the oral route via (gavage) and second, the dermal route. These routes are likely to be of more human relevance than the inhalative route due to the low vapour pressure of the substance.

Principles of method if other than guideline:

Method: other: Industrial acute inhalation toxicity test, groups of animals were exposed for 4h to graded air concentrations of the test substance and observed 14 days thereafter

GLP compliance:

no

Test type:

other: inhalation toxicity test, no further details

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Method of conditioning air: air was bubbled through the material and led directly into a chamber containing the animals, this results in an air stream near saturation; saturated vapor exposure

Duration of exposure:

6 h

Concentrations:

Only stated: saturated atmosphere (limited reporting); the calculated saturated vapour pressure is 10.4mg/L (based on vapour pressure 0.0013hPa at 20°C and the molecular weight 194.2g/mol) - an aerosol of the test substance might have been generated.

No. of animals per sex per dose:

no details reported

Sex:

not specified

Dose descriptor:

LC50

Effect level:

> 10.4 mg/L air (nominal)

Exp. duration:

6 h

Remarks on result:

other: no concentration/dose reported, only saturated vapor; calculation of concentration based on the molecular weight of the test substance (194.2g/mol); an aerosol might have been generated

Mortality:

There were no deaths when an unspecified number of rats were exposed to the saturated vapour for 6 h within observation period of 14 days.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 for acute inhalation toxicity is greater than 10.4 mg/L/6h at saturated vapor.

Executive summary:

The study is not assignable, only published in a short table (secondary literature) and reporting is very limited (non-GLP study). Acute inhalation toxicity (6h saturated vapor) was tested in rats, no mortalities were observed within 14 days. However, an aerosol might have been generated.

The LD50 for acute inhalation toxicity is greater than 10.4 mg/L/6h at saturated vapor.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

10 400 mg/m³ air

Quality of whole database:

Concentration calculated - corresponds to saturated vapour concentration

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is acceptable with restrictions and sufficient for endpoint evaluation. Restrictions are limited reporting (non-GLP study).

Principles of method if other than guideline:

Method: A method of Draize et al. (1944) was followed. Neat material was held in contact with clipped skin for 24h (occlusive) by a rubber sleeve. Prior to exposure the subjects are prepared by clipping the skin of the trunk free of hair. Approximately half of the animals are further prepared by making epidermal abrasions longitudinally over the area of exposure two centimeters apart. Depilation or shaving causes sufficient disturbance of the stratum corneum so that a 24h period is necessary for the recovery of the skin before exposure to the agent. Clipping the hair with small animal clippers was preferred since the intact skin remains undisturbed. The sleeve is slipped onto the animal which is then placed in a comfortable but immobilized position in a multiple animal holder. The doses of liquids and solutions are calculated on tile basis of body weight and introduced under the sleeve.

GLP compliance:

no

Test type:

other: historical test according to Draize et al. (1944)

Limit test:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): Dimethyl phthalate; CAS-No.: 131-11-3
- Other: no further data

Species:

rabbit

Strain:

not specified

Sex:

not specified

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Doses:

- 3.9, 6.0 and 9.4 ml/kg bw in a preliminary range finding
- during the main test, graded dose grops were applied; no further details on single doses given

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: blood morphology

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 12 000 mg/kg bw

Remarks on result:

other: calculated from original data 10 ml/kg (density 1.194 g/ml)

Conclusions:

LD50 in rabbit for acute dermal  toxicity of >12000 mg/kg bw was reported (original data: LD50 >=10 ml/kg bw, density 1.194 g/ml).

Executive summary:

The study is sufficient for endpoint evaluation with acceptable restrictions due to limited reporting (non-GLP study). Test substance was tested in rabbits (undiluted test substance) for acute dermal toxicity.

An LD50 in rabbit for acute dermal  toxicity of >12000 mg/kg bw was reported (original data: LD50 >10 ml/kg bw, density 1.194 g/ml).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

12 000 mg/kg bw

Additional information

Oral exposure route:

In an acute toxicity study conducted by Draize et al. [1948], DMP was not acutely toxic via (LD50 rat, oral = 8200 mg/kg bw; original data: LD50 = 6.9 ml/kg bw, calculation based on density 1.194 g/ml). In this studygroups of 10 rats were administered various doses of neat test material via gavage. Mortalities occurred, signs of intoxication in the rat included drowsiness within the first 15 min after an acute oral dose. Animals rapidly became semi-conscious, deaths occurred between 7 h and 3 days. In a toxicological review by Krauskopf [1973], LD50 values in rat ranged from 6700 to 6900 mg/kg bw (Krauskopf, 1973 and references cited therein). A study from Union Carbide (TSCAT OTS0533903, 1987) reported a combined LD50 for male and female of 5120 mg/kg bw after oral gavage of a DMP mixture (85%). An overview of further LD50 values in various species (guinea pig, chicken and mouse) is given in Table 1.

Table 1. Acute toxicity studies – overview of studies that are adequate for endpoint evaluation

Species	Results (LD50/LC50)	References
Oral
Rat	6.9 ml/kg bw (8200 mg/kg bw)	Draize et al. [1948]
Rabbit	4.4 ml/kg bw (5300 mg/kg bw)	Draize et al. [1948]
Guinea pig	2.4 ml/kg bw (2900 mg/kg bw)	Draize et al. [1948]
Chick	8.5 ml/kg bw (10200 mg/kg bw)	Draize et al. [1948]
Mouse	7.2 ml/kg bw (8600 mg/kg bw)	Draize et al. [1948]

Inhalative exposure route:

Saturated vapour was tested via inhalative route of exposure (as calculated on vapour pressure of the substance) in rats (no further details on strain and sex). The calculated saturated vapour pressure is 10.4 mg/L (based on vapour pressure 0.0013 hPa at 20°C and the molecular weight 194.2 g/mol) - an aerosol of the test substance might have been generated. No mortalities were observed when unspecified numbers of rats were exposed to the saturated vapour for 6 h within an observation period of 14 days. An LC0 = 10.40 mg/kg bw can be derived, an LD50 could not be determined. However, a reliable key study with restrictions (non-GLP studies) is available for the first, the oral route via (gavage) and there is also one covering the second, the dermal route. These routes are more likely to be of human relevance compared to the inhalative route. In an other study, cats survived a 6.5 h exposure to a DMP mist of 2.0 mg/L but one of two cats died when the concentration was increased to 10.2 mg/L [Levinskas, 1973].

Dermal exposure route:

A historical method described by Draize et al. [1944] was followed. Neat material was held in contact with clipped skin for 24h (occlusive) by a rubber sleeve. The doses of liquids and solutions are calculated on tile basis of body weight and introduced under the sleeve. The estimated LD50 dermal is greater than >12000 mg/kg bw (calculated based on original data: 10 ml/kg bw; density 1.194 g/ml) determined in rabbits [Draize et al., 1948]. Additionally, dermal LD50 values noted by ECB [2000] range from > 4800 mg/kg bw in guinea pigs to 38000 mg/kg bw in rats.

Conclusion:

Taking all the presented data into consideration, dimethyl phthalate was concluded to be of low toxicity after a single ingestion, after short-term inhalation and short-term skin contact. The inhalation of a highly enriched/saturated vapor-air-mixture represents an unlikely acute hazard.

Justification for classification or non-classification

GHS classification (GHS UN rev.2, 2007):

- Oral route: no classification required

- Dermal route: no classification required

- Inhalation route (vapour, dust): no classification required