Registration Dossier

Administrative data

Description of key information

It should be noted that all tests performed in the past, have used the 50% aqueous solution which is the marketed product.
Acute toxicity: oral:
A K1 acute oral toxicity test was performed in male and female Sprague Dawley rats according to a guideline similar to OECD Guideline 401 (Mallory VT, 1981). This study was selected as key study. In addition, a supporting K2 study was available (Vinegar MB, 1977).
Acute toxicity: inhalation
No reliable data were available. However, this endpoint is waived as specific data are available for the oral and dermal exposure route.
Acute toxicity: dermal
A K1 acute dermal toxicity test was performed in male and female New Zealand White rabbits according to a guideline similar to OECD Guideline 402 (Auletta CS, 1981). This study was selected as key study.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
4 600 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
4 000 mg/kg bw

Additional information

Acute toxicity: oral

Mallory VT (1981) investigated the acute oral toxicity via gavage of 7000, 8000, 9000 and 10000 mg/kg bw NMMO in male/female Sprague-Dawley rats (5 animals per sex and per dose), using an aqueous solution containing 50% NMMO. After 14 days of observation, none of the animals died at the 7000 mg/kg dose level, two of the ten died at the 8000 mg/kg dose level (2 females), three of ten died at the 9000 mg/kg dose level (1 male, 2 females) and seven of ten died at the 10000 mg/kg dose level (3 males and 4 females). The acute oral LD50 value was observed to be 9200 mg/kg bw. The test solution used was a 50% aqueous solution of NMMO. The LD50 of the pure NMMO is therefore considered to be 4600 mg/kg. Clinical signs included diarrhea, piloerection, abnormal gait, abnormal stance, decreased body tone, decreased activity and orange discoloration around the nose and genital areas. Necropsy revealed distended fluid-filled stomachs and intestines (clear, tan, green, white or orange), mottled lungs, darkened thymuses and darkened lymph nodes. Terminal necropsy revealed no visible lesions in any of the remaining rats.

This study is designated as key study.

In addition, one supporting K2 study reported an LD50 value in male/female rats of > 10000 mg/kg bw, based on a 85% purity.

Acute toxicity: inhalation

No reliable studies were available for the inhalation route. A waiver statement was added and justified as following: next to the oral route of exposure, for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route (REACH Regulation, column 2 adaptation of Annex VIII). For NMMO, a key study is available for the dermal route of exposure. Therefore, an acute inhalation toxicity study should not be performed.

Acute toxicity: dermal

Auletta CS (1981) investigated acute dermal toxicity of NMMO in New Zealand White male/female rabbits (5 animals per sex and per dose) after 24 hours of exposure to 8000 mg/kg bw. After 14 days of observation, an LD50 value of > 8000 mg/kg bw was reported. As a 50% aqueous solution is used, the LD50 for the pure NMMO is considered to be greater than 4000 mg/kg. All of the animals survived the fourteen-day post-dose period. Clinical signs observed during the limit test included soft stool, fecal staining and staining of the ano-genital area and were noted sporadically in single animals on days 1 and 2. Several animals exhibited nasal discharge between days 4 and 14. All animals exhibited weight losses or showed no change in weight at day 7, but all (except one female) gained weight between days 7 and 14. However, two of the males exhibited overall weight loss at day 14. In addition irritation was observed: after 24h animals exhibited well-defined or moderate to severe erhythema, generally with very slight or slight edema.

Observations made at necropsy were similar to those seen in control animals in the laboratory or were considered to represent normal physiologic variations.

Justification for classification or non-classification

Based on the available data and according to the DSD and CLP criteria NMMO should not be classified for acute oral and dermal toxicity.

No data were available to decide on the classification for the inhalation route.