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Description of key information

The oral rat LD50 was approx. 5325 mg/kg bw in a pre-guideline study that was conducted similar to the method described in OECD TG 401.
The inhalation LC50 is > 21 mg/L (4 hr, in the atmosphere generated using an evaporator heated to 100-210°C).
The acute dermal LD50 in rats is estimated to be > 3000 mg/kg bw, based on two independent OECD TG 411 90-day repeated dose rat studies.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 325 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
21 000 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 000 mg/kg bw

Additional information

Oral toxicity

The oral LD50was approximately 5325 mg/kg bw in male and female Heigl rats (5 animals/sex/dose; observation period 14 days) receiving formamide as aqueous solutions by oral gavage in a pre-guideline study that was essentially conducted similar to the OECD No. 401 Guideline. Clinical signs (and mortalities) were seen in groups at 3600 mg/kgbw and above, and included poor general health state, ruffled fur, irregular respiration, apathy,atony, lateral recumbent position and reduced food consumption. Surviving rats appeared normal within 12-14 days after dosing. Late mortality up to 9 days after dosing was noted (Key study).

 

Similar values were reported in several other studies of lower reliability. A lower oral LD50-value of approx. 3200 mg/kg bw was obtained in a rat study where formamide dose levels of 1000 and 10,000 mg/kg bw were fed in water. Reported mortalities were 1/6 rats seven days after receiving the low dose, and 5/6 rats on the day of dosing at the high dose level. Mortalities were attributed to digestive tract irritation and liver injury. However, this study is not considered to be acceptable for assessment because the study report lacks important details, and because only two dose levels were tested. The large spacing factor of 10 is inadequate for a reliable determination of the LD50-value (TSCAT, 1983).

 

 

Dermal toxicity

No valid acute dermal toxicity study is known to exist. However, there were in total four deaths at the high dose level in two independent 90-day rat studies that were conducted according to OECD TG 411 using male and female Wistar rats. 1/20 high dose animals died in the first study where the animals received 0, 300, 1000, and 3000 mg/kg/day (Key study), and 3/20 high dose animals died in the second study where the doses were 0, 30, 100, and 3000 mg/kg/day (key study). The acute dermal LD50in rats is therefore clearly above 3000 mg/kg bw.

Inhalation toxicity

In an inhalation study that was conducted similar to OECD TG No. 403 and under GLP, 6 male Sprague-Dawley rats were exposed for 4 hours to mean analytical concentrations of 1.3, 2.0, 5.1, 14, 19, 21 mg/L. The test atmosphere was generated by metering the test material into a round-bottom flask heated to 100-210 deg C for concentrations less than 19 mg/L. The two highest atmospheric concentrations were generated with a nebulizer. Within the 14 day observation period mortality was observed in 1 animal in the 21 mg/L dose group. Clinical observations included lethargy, hunched posture, ocular and nasal discharges, partially-closed eyes, diarrhea, brown-stained perineum, and weight loss. Gross necropsy was not reported. The LC50 is considered to be > 21 mg/L (Key study).

In a supporting study, a pre-guideline Inhalation Hazard Test performed similar to OECD TG 403, 12 rats were exposed for 8 hours to formamide vapours near saturation. The concentration was not analytically determined. There were no mortalities, clinical signs of toxicity, or findings during necropsy. Thus there was no indication of an inhalation risk due to vapours of formamide at concentrations near saturation at 20°C.

The results indicate that the inhalation toxicity of formamide is low at maximum saturation concentrations (i.e. vapour only), and also if rats are exposed to a mixed vapour/aerosol atmosphere. It should be noted that the saturation concentration of formamide is approx. 0.055 mg/L at 20°C (AUER Technikum, 1988); may be calculated as follows:

Saturated Vapour Concentration [ppm] = [(vapour pressure of substance in mm Hg)/760 mm Hg] X 106,

followed by conversion into mg/m³:

Conc [ppm] = mole volume (=24.1 L at 20°C)/ molecular weight [grams] X Conc [mg/m³)

Justification for classification or non-classification

Acute oral, inhalation, and dermal toxicity: no classification suggested. Criteria of regulations 67/548/EC and 1272/2008/EC are not met.

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