Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
Overall assessment factor (AF):
1

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

No specific toxicology data have been obtained for this reaction mass. The systemic toxicology for this material, however, may be cross-read from structurally overlapping and/or closely related materials such as Tri- and Tetraethylene glycol, which are major parts of this mass, and Polyethylene glycol 200 and 400. The systemic DNEL therefore can be cross-read basically from Tri- and Tetraethyleneglycol.

The reaction mass may, dependend on the supplyer, also contain up to 3% NaOH. In that case the material has to be classified as Skin Corr. 1B and the acute local DNEL of NaOH (2 mg/m 3; US TLV) has to be observed.

The following DNELs were not derived:

Acute systemic inhalation: The reaction mass material needs not to be classified in terms of systemic inhalation toxicity. The LC50 of a related material (Triethylene glycol) was > 5200 mg/m3 (BRRC, 1991). Another related material (PEG 200) showed an LC 50 (6 hrs) of > 2500 mg/m3, the highest feasible concentration (Crook et al., 1981). 500 mg/m3 was the NOAEC in a 9-day inhalation study with TriEG (Ballantyne et al., 2006). There is also no oral toxicity in rats and no significant irritation potential. For TriEG there was a low potential of sensory irritation with an RD 50 in mice of 5140 mg/m3 (Ballantyne et al., 2006). The NaOH content (up to 3%) limits the exposure for acute inhalation. For this case, an acutelocal inhalation DNEL is proposed on the basis of the properties of NaOH considering the US TLV of 2 mg/m3.

Dermal exposure (acute and chronic; local and systemic): No classification for dermal toxicity is warranted. On the other hand, the material may contain up to 3 % NaOH and in that case is to be classified as corrosive. No data are available which allow to propose a firm chronic DNEL for NaOH

Oral exposure: No classification for oral toxicity. The repeated dose toxicity has been investigated in oral (gavage) studies. No pronounced effects were noted with TetraEG in the course of a 28-day study with doses up to 2000 mg/kg bw/day (Schladt et. al., 1998) or in a 90-day study with PEG 400 (Hermansky et al., 1995) up to 5640 mg/kg bw/day and a NOAEL of 1128 mg/kg bw/day. Furthermore, there is no designed oral exposure; the reaction mass is not foreseen for an oral uptake in humans

 

DNEL- acute, inhalation, local:

Local irritation appears to be the effect which determines a DNEL for chronic exposure (see below). The local DNEL, however, should also be protective from systemic effects and this can be shown by the following consideration: subchronic dietary studies with Triethylene glycol and Tetraethylene glycol and PEG 400 are available. No pronounced effects were noted with TetraEG in the course of a 28 days study (NOAEL probably 2000 mg/kg bw and day; Schladt et al., 1998) nor with PEG 400 in a 90 days study (NOAEL was 1128 mg/kg bw and day; Hermansky et al.,1995) nor with TriEG in a 90 day study (NOAEL 1522 mg/kg bw and day; van Miller and Ballantyne, 2001). If 1128 mg/kg are combined with standard assessment factors (2 for time, 4 for allometric inter-species extrapolation and 5 for intra-species variation; resulting overall assessment factor 40) a virtual oral DNEL of 28 mg/kg bw/day would result. This dose, if distributed into the ambient air of an 8 hrs work-shift, is equivalent to a concentration of approximately 250 mg/m3, an aerosol of very high density. The local DNEL has to take into account a possible 3% NaOH content. For NaOH no chronic DNEL is available, therefore an acute inhalation DNEL for NaOH (2 mg/m3) is proposed on the basis of the US TLV for NaOH.

 

DNEL- long-term, inhalation, systemic:

TriEG has been investigated in a 9 days inhalation study and a NOAEC of 500 mg/m3 was recorded (Ballantyne et al., 2006). For the structurally related PEG 200 a NOAEC of 1000 mg/m3 has been obtained in a 90 days inahalation study (Crook et al., 1981). A comparison between both study indicates that exposure time does not play a major role and the time extrapolation factor may be kept low. A factor of 3 on the NOAEC in the Ballantyne study should be sufficiently conservative. The interspecies factor is 1 due to the inhalation route employed for these studies. The intrsspecies factor may be limited to 3 for the work place since the local effects are assumed to result from unspecific aerosol exposure without much enzymic involvement and interindividual variation. The resulting total assessment factor of 9 generates a DNEL of 50 mg/m3 /which is also the DNEL of TriEG on a a mg/m3 basis. This values appears to be compatible also with a chemosensory irritation study in which TriEG showed an RD50 in mice of 5140 mg/m3 (Ballantyne et al., 2006). It is pointed out that the pH of this material can be higher than 7 due to an NaOH content of up to 3%; under those conditions the US TLV for NaOH (2 mgm/m3; STEL value) is proposed as an acute DNEL. References: - Ballantyne et al., J.Appl.Toxicol. 26, 387 -396 (2006).- - Ballantyne and Snellings, J.Appl.Toxicol. 27, 291 -299 (2007).- - BRRC, Rep. 53 -139 (1991).- - Crook et al., Chemical Systems Laboratory, Rep.1L62622A554 (1981).- - Hermansky et al., Fd.Chem.Toxicol. 2, 139 -149 (1995).- - Schladt et al., Exp.Toxic.Pathol. 50, 257 -265 (1998).- - Van Miller and Ballantyne, Vet.Human.Toxicol. 43 (2001).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

No DNELs for the general population were proposed since there is no designed exposure of the public to this material.